Transgenic animals: catalysts in drug discovery

Authors

  • Anitha Rolla Department of Pharmacology, School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University Kakinada (JNTUK), Andhra Pradesh, India
  • Ankitha Kondepudi Department of Pharmacology, School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University Kakinada (JNTUK), Andhra Pradesh, India
  • Bhagya Lakshmi Meesala Department of Pharmacology, School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University Kakinada (JNTUK), Andhra Pradesh, India
  • Sridevi Korimelli Department of Pharmacology, School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University Kakinada (JNTUK), Andhra Pradesh, India
  • S. Ashok Krishnan Department of Pharmacology, School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University Kakinada (JNTUK), Andhra Pradesh, India
  • Sk. Kamar Jaha Department of Pharmacology, School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University Kakinada (JNTUK), Andhra Pradesh, India

Abstract

Transgenic technologies have fundamentally transformed scientific research by enabling precise genetic modifications with wide-ranging applications across various fields. This review examines the application of transgenic mice across various research domains including cancer, diabetes, cardiovascular science, neurology, gastrointestinal research, and reproductive science. We explored how these models are important in enhancing the knowledge of complex biological methods, from elucidating pathways of the disease to enhancing the quality of research outcomes in these fields. Key methodologies such as CRISPR-Cas9, TALENs, knock-out, knock-in, microinjection, embryonic stem (ES) cell transfection are highlighted, with a focus on their impact on experimental results. Additionally, the review addresses the use of various transgenic strains in drug discovery and the challenges associated with transgenic research. By integrated findings from multiple research areas, this review underscores the transformative potential of transgenic technologies and their pivotal role in driving innovation and addressing global challenges.

Keywords:

Gene knock out, Gene knock in, CRISPR-Cas9, genetically modified animals

DOI

https://doi.org/10.25004/IJPSDR.2024.160615

References

Shakweer WME, Krivoruchko AY, Dessouki SM, Khattab AA. A review of transgenic animal techniques and their applications. J Genet Eng Biotechnol [Internet]. 2023;21(1):55. Available from: http://dx.doi.org/10.1186/s43141-023-00502-z

Shakweer WME, Hafez YM, El-Sayed AA, Awadalla IM, Mohamed MI. Construction of ovine GH-pmKate2N expression vector and its uptake by ovine spermatozoa using different methods. J Genet Eng Biotechnol [Internet]. 2017;15(1):13–21. Available from: http://dx.doi.org/10.1016/j.jgeb.2017.04.001

Houdebine L-M. Use of transgenic animals to improve human health and animal production. Reprod Domest Anim [Internet]. 2005;40(4):269–81. Available from: http://dx.doi.org/10.1111/j.1439-0531.2005.00596.x

Cacheiro P, Spielmann N, Mashhadi HH, Fuchs H, Gailus-Durner V, Smedley D, et al. Knockout mice are an important tool for human monogenic heart disease studies. Dis Model Mech [Internet]. 2023;16(5). Available from: http://dx.doi.org/10.1242/dmm.049770

Hall B, Limaye A, Kulkarni AB. Overview: generation of gene knockout mice. Curr Protoc Cell Biol, 2009. Curr Protoc Cell Biol. 2009;19:19–31.

Li G, Zhang X, Wang H, Mo J, Zhong C, Shi J, et al. CRISPR/Cas9-mediated integration of large transgene into pig CEP112 locus. G3 (Bethesda) [Internet]. 2020;10(2):467–73. Available from: http://dx.doi.org/10.1534/g3.119.400810

Wang Y, Li J, Xiang J, Wen B, Mu H, Zhang W, et al. Highly efficient generation of biallelic reporter gene knock-in mice via CRISPR-mediated genome editing of ESCs. Protein Cell [Internet]. 2016;7(2):152–6. Available from: http://dx.doi.org/10.1007/s13238-015-0228-3

Verkoczy L, Alt FW, Tian M. Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies. Immunol Rev [Internet]. 2017;275(1):89–107. Available from: http://dx.doi.org/10.1111/imr.12505

Hobson-West P, Davies A. Societal sentience: Constructions of the public in animal research policy and practice: Constructions of the public in animal research policy and practice. Sci Technol Human Values [Internet]. 2018;43(4):671–93. Available from: http://dx.doi.org/10.1177/0162243917736138

Robinson NB, Krieger K, Khan FM, Huffman W, Chang M, Naik A, et al. The current state of animal models in research: A review. Int J Surg [Internet]. 2019;72:9–13. Available from: http://dx.doi.org/10.1016/j.ijsu.2019.10.015

Lee KH, Lee DW, Kang BC. The “R” principles in laboratory animal experiments. Lab Anim Res [Internet]. 2020;36(1):45. Available from: http://dx.doi.org/10.1186/s42826-020-00078-6

Baptista J, Faustino-Rocha AI, Oliveira PA. Animal Models in Pharmacology: A Brief History Awarding the Nobel Prizes for Physiology or Medicine. Pharmacology. 2021;106(7–8):356–68.

Swearengen JR. Choosing the right animal model for infectious disease research. Animal Model Exp Med [Internet]. 2018;1(2):100–8. Available from: http://dx.doi.org/10.1002/ame2.12020

Fernandes MR, Pedroso AR. Animal experimentation: A look into ethics, welfare and alternative methods. Rev Assoc Med Bras [Internet]. 2017;63(11):923–8. Available from: http://dx.doi.org/10.1590/1806-9282.63.11.923

Porret A, Mérillat A-M, Guichard S, Beermann F, Hummler E. Tissue-specific transgenic and knockout mice. Methods Mol Biol [Internet]. 2006;337:185–205. Available from: http://dx.doi.org/10.1385/1-59745-095-2:185

Li Y, Meng Q, Yang M, Liu D, Hou X, Tang L, et al. Current trends in drug metabolism and pharmacokinetics. Acta Pharm Sin B [Internet]. 2019;9(6):1113–44. Available from: http://dx.doi.org/10.1016/j.apsb.2019.10.001

Cheung C, Gonzalez FJ. Humanized mouse lines and their application for prediction of human drug metabolism and toxicological risk assessment. J Pharmacol Exp Ther [Internet]. 2008;327(2):288–99. Available from: http://dx.doi.org/10.1124/jpet.108.141242

Lister MF, Sharkey J, Sawatzky DA, Hodgkiss JP, Davidson DJ, Rossi AG, et al. The role of the purinergic P2X7 receptor in inflammation. J Inflamm (Lond) [Internet]. 2007;4(1):5. Available from: http://dx.doi.org/10.1186/1476-9255-4-5

Bunnage ME. Getting pharmaceutical R&D back on target. Nat Chem Biol [Internet]. 2011;7(6):335–9. Available from: http://dx.doi.org/10.1038/nchembio.581

Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol [Internet]. 2014;32(1):40–51. Available from: http://dx.doi.org/10.1038/nbt.2786

Jentzsch V, Osipenko L, Scannell JW, Hickman JA. Costs and causes of oncology drug attrition with the example of insulin-like growth factor-1 receptor inhibitors. JAMA Netw Open [Internet]. 2023;6(7):e2324977. Available from: http://dx.doi.org/10.1001/jamanetworkopen.2023.24977

Navarro-Serna S, Vilarino M, Park I, Gadea J, Ross PJ. Livestock gene editing by one-step embryo manipulation. J Equine Vet Sci [Internet]. 2020;89(103025):103025. Available from: http://dx.doi.org/10.1016/j.jevs.2020.103025

Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, et al. High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell [Internet]. 2015;163(6):1515–26. Available from: http://dx.doi.org/10.1016/j.cell.2015.11.015

Ancos-Pintado R, Bragado-García I, Morales ML, García-Vicente R, Arroyo-Barea A, Rodríguez-García A, et al. High-throughput CRISPR screening in hematological neoplasms. Cancers (Basel) [Internet]. 2022;14(15):3612. Available from: http://dx.doi.org/10.3390/cancers14153612

Shi J, Wang E, Milazzo JP, Wang Z, Kinney JB, Vakoc CR. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat Biotechnol [Internet]. 2015;33(6):661–7. Available from: http://dx.doi.org/10.1038/nbt.3235

Ormandy EH, Dale J, Griffin G. Genetic engineering of animals: ethical issues, including welfare concerns. Can Vet J. 2011;52(5):544–50.

Tannenbaum J, Bennett BT. Russell and Burch’s 3Rs then and now: the need for clarity in definition and purpose. J Am Assoc Lab Anim Sci. 2015;54(2):120–32.

Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev [Internet]. 2010;24(18):1967–2000. Available from: http://dx.doi.org/10.1101/gad.1965810

Buhmeida A, Pyrhönen S, Laato M, Collan Y. Prognostic factors in prostate cancer. Diagn Pathol [Internet]. 2006;1(1):4. Available from: http://dx.doi.org/10.1186/1746-1596-1-4

Gingrich JR, Barrios RJ, Morton RA, Boyce BF, DeMayo FJ, Finegold MJ, et al. Metastatic prostate cancer in a transgenic mouse. Cancer Res. 1996;56(18):4096–102.

Thomsen MK, Busk M. Pre-clinical models to study human prostate cancer [Internet]. Preprints. 2023. Available from: http://dx.doi.org/10.20944/preprints202307.1424.v1

Testa U, Castelli G, Pelosi E. Cellular and molecular mechanisms underlying prostate cancer development: Therapeutic implications. Medicines (Basel) [Internet]. 2019;6(3):82. Available from: http://dx.doi.org/10.3390/medicines6030082

Thummel C, Tjian R, Grodzicker T. Expression of SV40 T antigen under control of adenovirus promoters. Cell [Internet]. 1981;23(3):825–36. Available from: http://dx.doi.org/10.1016/0092-8674(81)90447-5

Cristofano D. Pten is essential for embryonic development and tumour suppression. Nat Genet. 1998;19(4):348–55.

Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I, et al. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol [Internet]. 1998;8(21):1169–78. Available from: http://dx.doi.org/10.1016/s0960-9822(07)00488-5

Carracedo A, Alimonti A, Pandolfi PP. PTEN level in tumor suppression: how much is too little? Cancer Res [Internet]. 2011;71(3):629–33. Available from: http://dx.doi.org/10.1158/0008-5472.CAN-10-2488

Aquila S, Santoro M, Caputo A, Panno ML, Pezzi V, De Amicis F. The tumor suppressor PTEN as molecular switch node regulating cell metabolism and autophagy: Implications in immune system and tumor microenvironment. Cells [Internet]. 2020;9(7):1725. Available from: http://dx.doi.org/10.3390/cells9071725

Kim MJ, Cardiff RD, Desai N, Banach-Petrosky WA, Parsons R, Shen MM, et al. Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis. Proc Natl Acad Sci U S A [Internet]. 2002;99(5):2884–9. Available from: http://dx.doi.org/10.1073/pnas.042688999

Antao AM, Ramakrishna S, Kim K-S. The role of Nkx3.1 in cancers and stemness. Int J Stem Cells [Internet]. 2021;14(2):168–79. Available from: http://dx.doi.org/10.15283/ijsc20121

Kratzer TB, Jemal A, Miller KD, Nash S, Wiggins C, Redwood D, et al. Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer. CA Cancer J Clin [Internet]. 2023;73(2):120–46. Available from: http://dx.doi.org/10.3322/caac.21757

Metzger-Filho O, Sun Z, Viale G, Price KN, Crivellari D, Snyder RD, et al. Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol [Internet]. 2013;31(25):3083–90. Available from: http://dx.doi.org/10.1200/JCO.2012.46.1574

Liu C-L, Huang W-C, Cheng S-P, Chen M-J, Lin C-H, Chang S-C, et al. Characterization of mammary tumors arising from MMTV-PyVT transgenic mice. Curr Issues Mol Biol [Internet]. 2023;45(6):4518–28. Available from: http://dx.doi.org/10.3390/cimb45060286

Lin EY, Jones JG, Li P, Zhu L, Whitney KD, Muller WJ, et al. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol [Internet]. 2003;163(5):2113–26. Available from: http://dx.doi.org/10.1016/S0002-9440(10)63568-7

Regua AT, Arrigo A, Doheny D, Wong GL, Lo H-W. Transgenic mouse models of breast cancer. Cancer Lett [Internet]. 2021;516:73–83. Available from: http://dx.doi.org/10.1016/j.canlet.2021.05.027

Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell [Internet]. 2003;113(6):685–700. Available from: http://dx.doi.org/10.1016/s0092-8674(03)00432-x

Siegel PM, Massagué J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer [Internet]. 2003;3(11):807–21. Available from: http://dx.doi.org/10.1038/nrc1208

Zhu Q, Maitra U, Johnston D, Lozano M, Dudley JP. The homeodomain protein CDP regulates mammary-specific gene transcription and tumorigenesis. Mol Cell Biol [Internet]. 2004;24(11):4810–23. Available from: http://dx.doi.org/10.1128/MCB.24.11.4810-4823.2004

Mink S, Härtig E, Jennewein P, Doppler W, Cato AC. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor. Mol Cell Biol [Internet]. 1992;12(11):4906–18. Available from: http://dx.doi.org/10.1128/mcb.12.11.4906-4918.1992

Rauner G. Using organoids to tap mammary gland diversity for novel insight. J Mammary Gland Biol Neoplasia [Internet]. 2024;29(1):7. Available from: http://dx.doi.org/10.1007/s10911-024-09559-z

Katoh M, Katoh M. Precision medicine for human cancers with Notch signaling dysregulation (Review). Int J Mol Med [Internet]. 2020;45(2):279–97. Available from: http://dx.doi.org/10.3892/ijmm.2019.4418

Ross SR. Mouse mammary tumor virus molecular biology and oncogenesis. Viruses [Internet]. 2010;2(9):2000–12. Available from: http://dx.doi.org/10.3390/v2092000

Smith JA, Barraclough R, Fernig DG, Rudland PS. Identification of alpha transforming growth factor as a possible local trophic agent for the mammary gland. J Cell Physiol [Internet]. 1989;141(2):362–70. Available from: http://dx.doi.org/10.1002/jcp.1041410218

Normanno N, Ciardiello F, Brandt R, Salomon DS. Epidermal growth factor-related peptides in the pathogenesis of human breast cancer. Breast Cancer Res Treat [Internet]. 1994;29(1):11–27. Available from: http://dx.doi.org/10.1007/bf00666178

Gasco M, Shami S, Crook T. The p53 pathway in breast cancer. Breast Cancer Res [Internet]. 2002;4(2):70–6. Available from: http://dx.doi.org/10.1186/bcr426

Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol [Internet]. 1994;4(1):1–7. Available from: http://dx.doi.org/10.1016/s0960-9822(00)00002-6

Harvey M, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A, Donehower LA. Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice. Nat Genet [Internet]. 1993;5(3):225–9. Available from: http://dx.doi.org/10.1038/ng1193-225

Engel BE, Cress WD, Santiago-Cardona PG. The retinoblastoma protein: A master tumor suppressor acts as a link between cell cycle and cell adhesion. Cell Health Cytoskelet [Internet]. 2015;7:1–10. Available from: http://dx.doi.org/10.2147/CHC.S28079

Herschkowitz JI, He X, Fan C, Perou CM. The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas. Breast Cancer Res [Internet]. 2008;10(5):R75. Available from: http://dx.doi.org/10.1186/bcr2142

Witkiewicz AK, Knudsen ES. Retinoblastoma tumor suppressor pathway in breast cancer: prognosis, precision medicine, and therapeutic interventions. Breast Cancer Res [Internet]. 2014;16(3):207. Available from: http://dx.doi.org/10.1186/bcr3652

Kanno A, Masamune A, Hanada K, Kikuyama M, Kitano M. Advances in Early Detection of Pancreatic Cancer. Diagnostics (Basel) [Internet]. 2019;9(1):18. Available from: http://dx.doi.org/10.3390/diagnostics9010018

Ferri-Borgogno S, Barui S, McGee AM, Griffiths T, Singh PK, Piett CG, et al. Paradoxical role of AT-rich interactive domain 1A in restraining pancreatic carcinogenesis. Cancers (Basel) [Internet]. 2020;12(9):2695. Available from: http://dx.doi.org/10.3390/cancers12092695

Kimura Y, Fukuda A, Ogawa S, Maruno T, Takada Y, Tsuda M, et al. ARID1A maintains differentiation of pancreatic ductal cells and inhibits development of pancreatic ductal adenocarcinoma in mice. Gastroenterology [Internet]. 2018;155(1):194-209.e2. Available from: http://dx.doi.org/10.1053/j.gastro.2018.03.039

Weng C-C, Lin Y-C, Cheng K-H. The use of genetically engineered mouse models for studying the function of mutated driver genes in pancreatic cancer. J Clin Med [Internet]. 2019;8(9):1369. Available from: http://dx.doi.org/10.3390/jcm8091369

Luo J. KRAS mutation in pancreatic cancer. Semin Oncol [Internet]. 2021;48(1):10–8. Available from: http://dx.doi.org/10.1053/j.seminoncol.2021.02.003

Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev [Internet]. 2003;17(24):3112–26. Available from: http://dx.doi.org/10.1101/gad.1158703

Lewis BC, Klimstra DS, Varmus HE. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer. Genes Dev [Internet]. 2003;17(24):3127–38. Available from: http://dx.doi.org/10.1101/gad.1140403

Riggs PK, Rho O, DiGiovanni J. Alteration of Egr-1 mRNA during multistage carcinogenesis in mouse skin. Mol Carcinog [Internet]. 2000;27(4):247–51. Available from: http://dx.doi.org/10.1002/(sici)1098-2744(200004)27:4<247::aid-mc1>3.0.co;2-4

Abel EL, Angel JM, Kiguchi K, DiGiovanni J. Multi-stage chemical carcinogenesis in mouse skin: fundamentals and applications. Nat Protoc [Internet]. 2009;4(9):1350–62. Available from: http://dx.doi.org/10.1038/nprot.2009.120

Coussens LM, Hanahan D, Arbeit JM. Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice. Am J Pathol. 1996;149(6):1899–917.

Peixoto da Silva S, Santos JMO, Mestre VF, Medeiros-Fonseca B, Oliveira PA, M S M Bastos M, et al. Human Papillomavirus 16-transgenic mice as a model to study cancer-associated cachexia. Int J Mol Sci [Internet]. 2020;21(14):5020. Available from: http://dx.doi.org/10.3390/ijms21145020

Cochicho D, Nunes A, Gomes JP, Martins L, Cunha M, Medeiros-Fonseca B, et al. Characterization of the human Papillomavirus 16 oncogenes in K14HPV16 mice: Sublineage A1 drives multi-organ carcinogenesis. Int J Mol Sci [Internet]. 2022;23(20):12371. Available from: http://dx.doi.org/10.3390/ijms232012371

Zhang X, Bolt M, Guertin MJ, Chen W, Zhang S, Cherrington BD, et al. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation. Proc Natl Acad Sci U S A [Internet]. 2012;109(33):13331–6. Available from: http://dx.doi.org/10.1073/pnas.1203280109

Schinko JB, Weber M, Viktorinova I, Kiupakis A, Averof M, Klingler M, et al. Functionality of the GAL4/UAS system in Tribolium requires the use of endogenous core promoters. BMC Dev Biol [Internet]. 2010;10(1):53. Available from: http://dx.doi.org/10.1186/1471-213X-10-53

Zhang T, Dutton-Regester K, Brown KM, Hayward NK. The genomic landscape of cutaneous melanoma. Pigment Cell Melanoma Res [Internet]. 2016;29(3):266–83. Available from: http://dx.doi.org/10.1111/pcmr.12459

Powell MB, Hyman P, Bell OD, Balmain A, Brown K, Alberts D, et al. Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 Ha-ras gene regulated by a mouse tyrosinase promoter. Mol Carcinog [Internet]. 1995;12(2):82–90. Available from: http://dx.doi.org/10.1002/mc.2940120205

Battaglia L, Scomparin A, Dianzani C, Milla P, Muntoni E, Arpicco S, et al. Nanotechnology addressing cutaneous melanoma: The Italian landscape. Pharmaceutics [Internet]. 2021;13(10):1617. Available from: http://dx.doi.org/10.3390/pharmaceutics13101617

Zhang J, Zhao J, Jiang W-J, Shan X-W, Yang X-M, Gao J-G. Conditional gene manipulation: Cre-ating a new biological era. J Zhejiang Univ Sci B [Internet]. 2012;13(7):511–24. Available from: http://dx.doi.org/10.1631/jzus.B1200042

Chen D, Thayer TC, Wen L, Wong FS. Mouse models of autoimmune diabetes: The nonobese diabetic (NOD) mouse. Methods Mol Biol [Internet]. 2020;2128:87–92. Available from: http://dx.doi.org/10.1007/978-1-0716-0385-7_6

Niu L, Xu Y-C, Dai Z, Tang H-Q. Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene. World J Gastroenterol [Internet]. 2008;14(26):4209–15. Available from: http://dx.doi.org/10.3748/wjg.14.4209

Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell [Internet]. 1996;84(3):491–5. Available from: http://dx.doi.org/10.1016/s0092-8674(00)81294-5

Suriano F, Vieira-Silva S, Falony G, Roumain M, Paquot A, Pelicaen R, et al. Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin. Microbiome [Internet]. 2021;9(1):147. Available from: http://dx.doi.org/10.1186/s40168-021-01097-8

Vatashchuk MV, Bayliak MM, Hurza VV, Storey KB, Lushchak VI. Metabolic syndrome: Lessons from rodent and Drosophila models. Biomed Res Int [Internet]. 2022;2022:5850507. Available from: http://dx.doi.org/10.1155/2022/5850507

de Luca C, Kowalski TJ, Zhang Y, Elmquist JK, Lee C, Kilimann MW, et al. Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest [Internet]. 2005;115(12):3484–93. Available from: http://dx.doi.org/10.1172/JCI24059

Tartaglia LA. The leptin receptor. J Biol Chem [Internet]. 1997;272(10):6093–6. Available from: http://dx.doi.org/10.1074/jbc.272.10.6093

Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu [Internet]. 1980;29(1):1–13. Available from: http://dx.doi.org/10.1538/expanim1978.29.1_1

Cai X, McGinnis JF. Diabetic retinopathy: Animal models, therapies, and perspectives. J Diabetes Res [Internet]. 2016;2016:3789217. Available from: http://dx.doi.org/10.1155/2016/3789217

Klebig ML, Wilkinson JE, Geisler JG, Woychik RP. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur. Proc Natl Acad Sci U S A [Internet]. 1995;92(11):4728–32. Available from: http://dx.doi.org/10.1073/pnas.92.11.4728

Pandey S, Dvorakova MC, Pandey S, Dvorakova MC. Future Perspective of Diabetic Animal Models. Endocr Metab Immune Disord Drug Targets. Endocr Metab Immune Disord Drug Targets. 2020;20(1):25–38.

Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome: Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci [Internet]. 2010;1212(1):E1–19. Available from: http://dx.doi.org/10.1111/j.1749-6632.2010.05875.x

Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab [Internet]. 2004;89(6):2548–56. Available from: http://dx.doi.org/10.1210/jc.2004-0395

Arioglu E, Rother KI, Reitman ML, Premkumar A, Taylor SI. Lipoatrophy syndromes: when “too little fat” is a clinical problem: Lipoatrophy syndromes. Pediatr Diabetes [Internet]. 2000;1(3):155–68. Available from: http://dx.doi.org/10.1034/j.1399-5448.2000.010307.x

Friedman J. The long road to leptin. J Clin Invest [Internet]. 2016;126(12):4727–34. Available from: http://dx.doi.org/10.1172/JCI91578

Chandrasekaran P, Weiskirchen R. The role of obesity in type 2 diabetes mellitus-an overview. Int J Mol Sci [Internet]. 2024;25(3):1882. Available from: http://dx.doi.org/10.3390/ijms25031882

Reifsnyder PC, Churchill G, Leiter EH. Maternal environment and genotype interact to establish diabesity in mice. Genome Res [Internet]. 2000;10(10):1568–78. Available from: http://dx.doi.org/10.1101/gr.147000

Kim JH, Saxton AM. The TALLYHO mouse as a model of human type 2 diabetes. Methods Mol Biol [Internet]. 2012;933:75–87. Available from: http://dx.doi.org/10.1007/978-1-62703-068-7_6

Parilla JH, Willard JR, Barrow BM, Zraika S. A mouse model of beta-cell dysfunction as seen in human type 2 diabetes. J Diabetes Res [Internet]. 2018;2018:6106051. Available from: http://dx.doi.org/10.1155/2018/6106051

Wauman J, Zabeau L, Tavernier J. The Leptin Receptor Complex: Heavier Than Expected? Front Endocrinol (Lausanne). 2017.

Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palù G, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol [Internet]. 2007;292(2):G518-25. Available from: http://dx.doi.org/10.1152/ajpgi.00024.2006

Geurts L, Lazarevic V, Derrien M, Everard A, Van Roye M, Knauf C, et al. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue. Front Microbiol [Internet]. 2011;2:149. Available from: http://dx.doi.org/10.3389/fmicb.2011.00149

Coleman DL. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia [Internet]. 1978;14(3):141–8. Available from: http://dx.doi.org/10.1007/bf00429772

Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science [Internet]. 1995;269(5223):540–3. Available from: http://dx.doi.org/10.1126/science.7624776

Simon DB, Lifton RP. Mutations in Na(K)Cl transporters in Gitelman’s and Bartter’s syndromes. Curr Opin Cell Biol [Internet]. 1998;10(4):450–4. Available from: http://dx.doi.org/10.1016/s0955-0674(98)80057-4

Crisan D, Carr J. Angiotensin I-converting enzyme: genotype and disease associations. J Mol Diagn [Internet]. 2000;2(3):105–15. Available from: http://dx.doi.org/10.1016/S1525-1578(10)60624-1

Getz GS, Reardon CA. Do the apoe-/- and Ldlr-/- mice yield the same insight on atherogenesis? Arterioscler Thromb Vasc Biol [Internet]. 2016;36(9):1734–41. Available from: http://dx.doi.org/10.1161/ATVBAHA.116.306874

Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science [Internet]. 1992;258(5081):468–71. Available from: http://dx.doi.org/10.1126/science.1411543

Ishibashi S, Brown MS, Goldstein JL, Gerard RD, Hammer RE, Herz J. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J Clin Invest [Internet]. 1993;92(2):883–93. Available from: http://dx.doi.org/10.1172/JCI116663

Roselaar SE, Kakkanathu PX, Daugherty A. Lymphocyte populations in atherosclerotic lesions of apoE -/- and LDL receptor -/- mice. Decreasing density with disease progression: Decreasing density with disease progression. Arterioscler Thromb Vasc Biol [Internet]. 1996;16(8):1013–8. Available from: http://dx.doi.org/10.1161/01.atv.16.8.1013

Stylianou IM, Bauer RC, Reilly MP, Rader DJ. Genetic basis of atherosclerosis: insights from mice and humans. Circ Res [Internet]. 2012;110(2):337–55. Available from: http://dx.doi.org/10.1161/CIRCRESAHA.110.230854

Hopkins PN. Molecular biology and genetics of atherosclerosis. In: Preventive Cardiology: Companion to Braunwald’s Heart Disease. Elsevier; 2011. p. 86–120.

Staršíchová A. SR-B1-/-ApoE-R61h/h mice mimic human coronary heart disease. Cardiovasc Drugs Ther [Internet]. 2023; Available from: http://dx.doi.org/10.1007/s10557-023-07475-8

Getz GS, Reardon CA. Insights from Murine studies on the site specificity of atherosclerosis. Int J Mol Sci [Internet]. 2024;25(12):6375. Available from: http://dx.doi.org/10.3390/ijms25126375

Miao L-N, Pan D, Shi J, Du J-P, Chen P-F, Gao J, et al. Role and mechanism of PKC-δ for cardiovascular disease: Current status and perspective. Front Cardiovasc Med [Internet]. 2022;9:816369. Available from: http://dx.doi.org/10.3389/fcvm.2022.816369

Jones LR, Suzuki YJ, Wang W, Kobayashi YM, Ramesh V, Franzini-Armstrong C, et al. Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. J Clin Invest [Internet]. 1998;101(7):1385–93. Available from: http://dx.doi.org/10.1172/JCI1362

Bisping E, Ikeda S, Kong SW, Tarnavski O, Bodyak N, McMullen JR, et al. Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure. Proc Natl Acad Sci U S A [Internet]. 2006;103(39):14471–6. Available from: http://dx.doi.org/10.1073/pnas.0602543103

Wilson RJ, Drake JC, Cui D, Zhang M, Perry HM, Kashatus JA, et al. Conditional MitoTimer reporter mice for assessment of mitochondrial structure, oxidative stress, and mitophagy. Mitochondrion [Internet]. 2019;44:20–6. Available from: http://dx.doi.org/10.1016/j.mito.2017.12.008

Kawaguchi A, Miyata T, Sawamoto K, Takashita N, Murayama A, Akamatsu W, et al. Nestin-EGFP transgenic mice: visualization of the self-renewal and multipotency of CNS stem cells. Mol Cell Neurosci [Internet]. 2001;17(2):259–73. Available from: http://dx.doi.org/10.1006/mcne.2000.0925

Chen W, Hu Y, Ju D. Gene therapy for neurodegenerative disorders: advances, insights and prospects. Acta Pharm Sin B [Internet]. 2020;10(8):1347–59. Available from: http://dx.doi.org/10.1016/j.apsb.2020.01.015

Lee JH, Wang J-H, Chen J, Li F, Edwards TL, Hewitt AW, et al. Gene therapy for visual loss: Opportunities and concerns. Prog Retin Eye Res [Internet]. 2019;68:31–53. Available from: http://dx.doi.org/10.1016/j.preteyeres.2018.08.003

Ehmke T, Leckelt J, Reichard M, Weiss H, Hovakimyan M, Heisterkamp A, et al. In vivo nonlinear imaging of corneal structures with special focus on BALB/c and streptozotocin-diabetic Thy1-YFP mice. Exp Eye Res [Internet]. 2016;146:137–44. Available from: http://dx.doi.org/10.1016/j.exer.2015.11.024

Vetrivel KS, Zhang Y-W, Xu H, Thinakaran G. Pathological and physiological functions of presenilins. Mol Neurodegener [Internet]. 2006;1(1):4. Available from: http://dx.doi.org/10.1186/1750-1326-1-4

Zhu Y-L, Sun M-F, Jia X-B, Cheng K, Xu Y-D, Zhou Z-L, et al. Neuroprotective effects of Astilbin on MPTP-induced Parkinson’s disease mice: Glial reaction, α-synuclein expression and oxidative stress. Int Immunopharmacol [Internet]. 2019;66:19–27. Available from: http://dx.doi.org/10.1016/j.intimp.2018.11.004

Liu C, Xie W, Gui C, Du Y. Pronuclear microinjection and oviduct transfer procedures for transgenic mouse production. Methods Mol Biol [Internet]. 2013;1027:217–32. Available from: http://dx.doi.org/10.1007/978-1-60327-369-5_10

Ballatore C, Lee VM-Y, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci [Internet]. 2007;8(9):663–72. Available from: http://dx.doi.org/10.1038/nrn2194

Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol [Internet]. 2009;11(7):909–13. Available from: http://dx.doi.org/10.1038/ncb1901

Kaufman SK, Sanders DW, Thomas TL, Ruchinskas AJ, Vaquer-Alicea J, Sharma AM, et al. Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. Neuron [Internet]. 2016;92(4):796–812. Available from: http://dx.doi.org/10.1016/j.neuron.2016.09.055

Clavaguera F, Akatsu H, Fraser G, Crowther RA, Frank S, Hench J, et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci U S A [Internet]. 2013;110(23):9535–40. Available from: http://dx.doi.org/10.1073/pnas.1301175110

Gotz J. PL‐03‐03: Animal models for Alzheimer’s disease and frontotemporal dementia. Alzheimers Dement [Internet]. 2009;5(4S_Part_4):P118–P118. Available from: http://dx.doi.org/10.1016/j.jalz.2009.05.372

Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, et al. Intraneuronal Abeta42 accumulation in human brain. Am J Pathol [Internet]. 2000;156(1):15–20. Available from: http://dx.doi.org/10.1016/s0002-9440(10)64700-1

Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol [Internet]. 2010;119(5):523–41. Available from: http://dx.doi.org/10.1007/s00401-010-0679-9

Peggion C, Scalcon V, Massimino ML, Nies K, Lopreiato R, Rigobello MP, et al. SOD1 in ALS: Taking stock in pathogenic mechanisms and the role of glial and muscle cells. Antioxidants (Basel) [Internet]. 2022;11(4):614. Available from: http://dx.doi.org/10.3390/antiox11040614

Jaarsma D, Haasdijk ED, Grashorn JA, Hawkins R, van Duijn W, Verspaget HW, et al. Human Cu/Zn superoxide dismutase (SOD1) overexpression in mice causes mitochondrial vacuolization, axonal degeneration, and premature motoneuron death and accelerates motoneuron disease in mice expressing a familial amyotrophic lateral sclerosis mutant SOD1. Neurobiol Dis [Internet]. 2000;7(6 Pt B):623–43. Available from: http://dx.doi.org/10.1006/nbdi.2000.0299

Jonsson PA, Graffmo KS, Andersen PM, Brännström T, Lindberg M, Oliveberg M, et al. Disulphide-reduced superoxide dismutase-1 in CNS of transgenic amyotrophic lateral sclerosis models. Brain [Internet]. 2006;129(Pt 2):451–64. Available from: http://dx.doi.org/10.1093/brain/awh704

Baccili Cury Megid T, Farooq AR, Wang X, Elimova E. Gastric cancer: Molecular mechanisms, novel targets, and immunotherapies: From bench to clinical therapeutics. Cancers (Basel) [Internet]. 2023;15(20):5075. Available from: http://dx.doi.org/10.3390/cancers15205075

Zhang Q, Yang M, Zhang P, Wu B, Wei X, Li S. Deciphering gastric inflammation-induced tumorigenesis through multi-omics data and AI methods. Cancer Biol Med [Internet]. 2023;21(4). Available from: http://dx.doi.org/10.20892/j.issn.2095-3941.2023.0129

Fox JG, Rogers AB, Whary MT, Ge Z, Ohtani M, Jones EK, et al. Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 -/- C57BL6 x Sv129 Helicobacter pylori-infected mice. Am J Pathol [Internet]. 2007;171(5):1520–8. Available from: http://dx.doi.org/10.2353/ajpath.2007.070249

Halberg RB, Chen X, Amos-Landgraf JM, White A, Rasmussen K, Clipson L, et al. The pleiotropic phenotype of Apc mutations in the mouse: allele specificity and effects of the genetic background. Genetics [Internet]. 2008;180(1):601–9. Available from: http://dx.doi.org/10.1534/genetics.108.091967

Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci [Internet]. 2007;120(Pt 19):3327–35. Available from: http://dx.doi.org/10.1242/jcs.03485

Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell [Internet]. 1996;87(5):803–9. Available from: http://dx.doi.org/10.1016/s0092-8674(00)81988-1

Xue Y, Johnson R, Desmet M, Snyder PW, Fleet JC. Generation of a transgenic mouse for colorectal cancer research with intestinal cre expression limited to the large intestine. Mol Cancer Res [Internet]. 2010;8(8):1095–104. Available from: http://dx.doi.org/10.1158/1541-7786.MCR-10-0195

Colnot S, Niwa-Kawakita M, Hamard G, Godard C, Le Plenier S, Houbron C, et al. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab Invest [Internet]. 2004;84(12):1619–30. Available from: http://dx.doi.org/10.1038/labinvest.3700180

Fleet JC, Wood RJ. Specific 1,25(OH)2D3-mediated regulation of transcellular calcium transport in Caco-2 cells. Am J Physiol [Internet]. 1999;276(4):G958-64. Available from: http://dx.doi.org/10.1152/ajpgi.1999.276.4.G958

Niu Z-S, Li B-K, Wang M. Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues. World J Gastroenterol [Internet]. 2002;8(5):822–6. Available from: http://dx.doi.org/10.3748/wjg.v8.i5.822

Xu C, Xu Z, Zhang Y, Evert M, Calvisi DF, Chen X. β-Catenin signaling in hepatocellular carcinoma. J Clin Invest [Internet]. 2022;132(4). Available from: http://dx.doi.org/10.1172/JCI154515

Kumar TR, Larson M, Wang H, McDermott J, Bronshteyn I. Transgenic mouse technology: principles and methods. Methods Mol Biol [Internet]. 2009;590:335–62. Available from: http://dx.doi.org/10.1007/978-1-60327-378-7_22

Brown SDM. Advances in mouse genetics for the study of human disease. Hum Mol Genet [Internet]. 2021;30(R2):R274–84. Available from: http://dx.doi.org/10.1093/hmg/ddab153

Published

30-11-2024
Statistics
Abstract Display: 115
PDF Downloads: 156
Dimension Badge

How to Cite

“Transgenic Animals: Catalysts in Drug Discovery”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 16, no. 6, Nov. 2024, pp. 1054-70, https://doi.org/10.25004/IJPSDR.2024.160615.

Issue

Section

Review Article

How to Cite

“Transgenic Animals: Catalysts in Drug Discovery”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 16, no. 6, Nov. 2024, pp. 1054-70, https://doi.org/10.25004/IJPSDR.2024.160615.

Similar Articles

1-10 of 137

You may also start an advanced similarity search for this article.