Review Of Genetically Modified Lines Of The Laboratory Animals Used As Model Metabolic Syndrome And Diabetes Mellitus Models

Kovaleva M.A., Makarova M.N., Makarov V.G. HOUM OF PHARMACY Research-and-Production Association; 3, Zavodskaya St., Build. 245, Kuzmolovsky Urban-Type Settlement, Vsevolozhsky District, Leningrad Region 188663 e-mail: kovaleva.ma@doclinika.ru

Abstract

The prevalence of diabetes mellitus and metabolic syndrome annually increases progressively in modern society. It causes increased morbidity and mortality from delayed complications. Today, metabolic pathologies are socially significant diseases leading to deterioration of the patient's quality of life. The use of adequate experimental models makes it possible to understand the causes of the development and mechanisms of diabetes mellitus and metabolic syndrome, to research the potential methods of their prevention and therapy. Referring to the metabolic syndrome, it should be noted that it is a multifactorial symptom complex of pathological changes, and the choice of the experimental model is fundamental for obtaining objective results. This review is devoted to the description of the most reliable and studied genetic models of diabetes mellitus and metabolic syndrome, systematized in reference to the type of laboratory animals. It shows the main characteristics, including biochemical, of mouse and rat lines, which characterize the state of carbohydrate (glucose and insulin concentration), lipid metabolism (concentration of cholesterol and triglycerides), energy metabolism (leptin). The mouse line with Lepob/obleptin deficiency, the mouse and rat lines with LepRdb/dbleptin deficiency, Zucker fatty rats, Zucker Diabetic Fatty rats, substrains of Spontaneoulsy hypertensive rats, Obese spontaneously hypertensive rats/Koletsky rats and SHR/NDmc-corpulent rats. Transgenic mice: MC4R - / -, Agouti yellow, KKAy/a, which are characterized by the development of resistance to leptin due to a defect in the transmission of the leptin signal to the cell, are also considered. The biometric parameters of blood pressure are also given for rats. The given information is about the changes of key characteristics, depending on sex and age of the laboratory animals. Each of the examined rodent lines has specific properties specific to diabetes mellitus and metabolic syndrome, which allows to study in detail the mechanisms of the development of pathologies, as well as potential drugs for the therapy of these diseases.

References

  1. de Artinano A.A., Castro M.M. Experimental rat models to study the metabolic syndrome. British Journal of Nutrition. 2009. Vol. 102: 1246–53.
  2. Zucker T.F., Zucker L.M. Hereditary obesity in the rat associated with high serum fat and cholesterol. Society for experimental biologyand medicine. 1962. Vol. 110: 165–71.
  3. Ouchi N., Kihara S., Funahashi T., Matsuzawa Y., Walsh K. Obesity, adiponectin and vascular inflammatory disease. Current Opinion in Lipidology. 2003. Vol. 14: 561–6.
  4. Picchi A., Gao X., Belmadani S., Potter B.J., Focardi M., Chilian W.M., Zhang C. Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome. Circulation Research. 2006. Vol. 99: 69–77.
  5. Wang B., Chandrasekera C., Pippin J.J. Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes. Current Diabetes Reviews. 2014. Vol. 10: 131–45.
  6. Simmons R.K., Alberti K.G., Gale E.A. et al. The metabolic syndrome: useful concept or clinical tool? Report of a WHO expert consultation. Diabetologia. 2010. Vol. 53 (4): 600–5.
  7. Janssen S.W.J., Martens G.J.M., (Fred) Sweep C.G.J., Ross H.A., Hermus A.R.M.M. In Zucker Diabetic Fatty Rats Plasma Leptin Levels are Correlated with Plasma Insulin Levels rather than with Body Weight. Hormone and Metabolic Research. 1999. Vol. 31: 610–5.
  8. Clark J.B., Palmer C.J., Shaw W.N. The diabetic Zucker fatty rat. Society for Experimental Biologyand Medicine. 1983. Vol. 173 (1): 68–75.
  9. Srinivasan K., Ramarao P. Animal models in type 2 diabetes research: An overview. Indian journal of medical research. 2007. Vol. 125: 451–72.
  10. Leshhenko D.V., Kostyuk N.V., Belyakova M.B., Egorova E.N., Minyaev M.V., Petrova M.B. Dieticheski inducirovannye zhivotnye modeli metabolicheskogo sindroma (obzor literatury). Verhnevolzhskiy medecinskiy zhurnal. 2015. T. 14 (2): 34–9.
  11. Ernsberger P., Koletsky R.J. The Glucose Tolerance Test as a Laboratory Tool with Clinical Implications. INTECH. 2012: 3–14.
  12. Kastin A.J., Pan W., Maness L.M. Koletsky R.J., Ernsberger P. Decreased transport of leptin across the blood-brain barrier in rats lacking the short form of the leptin receptor. Peptides. 1999. Vol. 20: 1449–53.
  13. Turley SD & Hansen CT (1986) Rates of sterol synthesis in the liver and extrahepatic tissues of the SHR/N-corpulent rat, an animal with hyperlipidemia and insulin-independent diabetes. Journal of lipid research. 1986. Vol. 27: 486–96.
  14. Hariya N., Mochizuki K., Inoue S., Morioka K., Shimada M., Okuda T., Goda T. Insulin Resistance in SHR/NDmc-cp Rats Correlates with Enlarged Perivascular Adipocytes and Endothelial Cell Dysfunction in Skeletal Muscle. Journal of Nutritional Science and Vitaminology. 2014. Vol. 60 (1): 52–9.
  15. Charles River. Research model. E`lektronnyy resurs [https://www.criver.com
  16. Tong Y.C., Wang C.J., Cheng J.T. The role of nitric oxide in the control of plasma glucose concentration in spontaneously hypertensive rats. Neuroscience Letters. 1997. Vol. 233 (2–3): 93–6.
  17. Kurtz T.W., Morris R.C. Biological Variability in Wistar-Kyoto Rats Implications for Research with the Spontaneously Hypertensive Rat. Hypertension. 1987. Vol. 10 (1): 127–31.
  18. Ingalls A.M., Dickie M.M., Snell G.D. (1950) Obese, a new mutation in the house mouse. Journal of Heredity. 1950. Vol. 41: 317–8.
  19. Katsuda Y., Ohta T., Shinohara M., Bin T., Yamada T. Diabetic mouse models. Open Journal of Animal Sciences. 2013. Vol. 3 (4): 334–42.
  20. Ioffe E., Moon B., Connolly E., Friedman J.M. Abnormal regulation of the leptin gene in the pathogenesis of obesity. Proceedings of the National Academy of Sciences. 1998. Vol. 95: 11852–7.
  21. Panchal S. K., Brown L. Rodent Models for Metabolic Syndrome Research. Journal of Biomedicine and Biotechnology. 2011. Article ID 351982. DOI:10.1155/2011/351982.
  22. Jung U.J., Lee M.-K., Park Y.B., Jeon S.-M., Choi M.-S. Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. Journal of pharmacology and experimental therapeutics august. 2006. – Vol. 318 (2): 476–83.
  23. Kennedy A. J., Ellacott K.L., King V. L., Hasty A. H. Mouse models of the metabolic syndrome. Disease Models and Mechanisms. 2010. Vol. 3 (4): 156–66.
  24. Ste Marie L., Miura G.I., Marsh D.J., Yagaloff K., Palmiter R.D. A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Proceedings of the National Academy of Sciences. 2000. Vol. 97: 12339–44.
  25. Tschop M., Heiman M.L. Rodent obesity models: an overview. Experimental and Clinical Endocrinology and Diabetes. 2001. Vol. 109: 307–19.
  26. Warbritton A., Gill A.M., Yen T.T., Bucci T., Wolff G. L. Pancreatic islet cells in preobese yellow Avy/- mice: relation to adult hyperinsulinemia and obesity. Proceedings of the Society for Experimental Biology and Medicine. 1994. Vol. 206: 145–51.
  27. Chakraborty G., Thumpayil S., Lafontant D.E. Woubneh W., Toney J.H. Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus. Lab Animal. 2009. Vol. 38: 364–8.
  28. Taketomi S., Tsuda M., Matsuo T., Iwatsuka H. and Suzuoki Z. Alternations of hepatic enzyme active- ties in KK and yellow KK mice with various diabetic states. Hormone and Metabolic Research. 1973. Vol. 5: 333–9.
  29. Hofman C., Lorenz K. and Colca J.R. Glucose transport deficiency in diabetic animals is corrected by treatment with oral antihyperglycemic agent pioglitazone. Endocrinology. 1991. Vol. 129: 1915–25.
  30. Koranyi L., James D., Mueckler M., Permutt M.A. Glucose Transporter Levels in Spontaneously Obese (db/db) Insulin-resistant Mice. European Journal of Clinical Investigation. 1990. Vol. 85: 962–7
  31. Kuklin A.I., Mynatt R.L., Klebig M.L., Kiefer L.L., Wilkison W.O., Woychik R.P., Michaud E.J. Liver-specific expression of the Agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes. Molecular Cancer. 2004. Vol. 3 (17): 1–10.
  32. The Jackson Laboratory. Strain datasheet. E`lektronnyy resurs [https://www.jax.org]

You may be interested