Liver, renal and subcutaneous histopathology in PEPCK-bGH transgenic pigs
Tóm tắt
Transgenic pigs were created that harboured a phosphoenol pyruvate carboxykinase-bovine growth hormone construct (PEPCK-bGH). Four founder animals and two transgenic offspring from one line were evaluated between 61/2 and 12 months of age. There was no evidence of severe hepatic or renal lesions in these pigs, which characterised transgenic PEPCK-bGH mice previously described. While glomerular and tubular lesions in kidney sections were not identified in the transgenic pigs, mesangial cell proliferation was observed in two transgenic offspring from a single line. Additionally, glomerular size was significantly increased in four of four puberal transgenic swine when compared to age- and sex-matched controls (28.30±4.1 vs. 14.2±2.7×105 μm3; representing 3 transgenic lines,p<0.05). Surprisingly, no mature adipocytes were observed in subcutaneous sections obtained in transgenic GH pigs. Histological evaluation of these transgenic pigs further illustrates the requirement for precise control of growth-related genes and their protein products.
Tài liệu tham khảo
Asa, S.L., Kovacs, K., Stefaneanu, L., Horvath, E., Billestrup, N., Gonzalez-Manchon, C. and Vale, W. (1990) Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone.Proc. Soc. Exp. Biol. Med. 193, 232–5.
Brem, G., Wanke, R., Wolf, E., Buchmuller, T., Muller, M., Brenig, B. and Hermanns, W. (1989) Multiple consequences of human growth hormone expression in transgenic mice.Mol. Biol. Med. 6, 531–47.
Doi, T., Striker, L.J., Gibson, C.C., Agodoa, L.Y.C., Brinster, R.L. and Striker, G.E. (1990) Glomerular lesions in mice transgeric for growth hormone and insulinlike growth factor-I.Am. J. Pathol. 137, 541–52.
Harris, D.M., Dunshea, F.R., Bauman, D.E., Boyd, R.D., Wang, S-Y., Johnson, R.A. and Clarke, S.D. (1993) Effect ofin vivo somatotropin treatment of growing pigs on adipose tissue lipogenesis.J. Anim. Sci. 71, 3293–300.
Martin, M.J. and Pinkert, C.A. (1994) Production of transgenic swine. In Pinkert, C.A. ed.,Transgenic Animal Technology: a Laboratory Handbook, pp. 315–38. Academic Press.
McGrane, M.M., deVente, J., Bloom, J., Park, E., Wynshaw-Boris, A., Wagner, T., Rottman, F.M. and Hanson, R.W. (1988) Tissue-specific expression and dietary regulation of a chimeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice.J. Biol. Chem. 263, 11443–51.
McGrane, M.M., Yun, J.S., Roesler, W.J., Park, E.A., Wagner, T.E. and Hanson, R.W. (1990) Developmental regulation and tissue-specific expression of a chimaeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic animals.J. Reprod. Fertil. Suppl.41, 17–23.
Orian, J.M., Tamakoshi, K., Mackay, I.R. and Brandon, M.R. (1990) New murine model for hepatocellular carcinoma: transgenic mice expressing metallothionein-ovine growth hormone fusion gene.J. Natl Cancer Inst. USA 82, 393–8.
Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, M.G., Birnberg, N.C. and Evans, R.M. (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes.Nature 300, 611–5.
Pinkert, C.A. (1991) Transgenic animals as models for metabolic and growth research.J. Anim. Sci. 69 (Suppl. 3), 49–55.
Pinkert, C.A., Dyer, T.J., Kooyman, D.L. and Kiehm, D.J. (1990) Characterization of transgenic livestock production.Dom. Anim. Endocrinol. 7, 1–18.
Pinkert, C.A., Ornitz, D.M., Brinster, R.L. and Palmiter, R.D. (1987) An albumin enhancer located 10 kb upstream functions along with its promoter to direct efficient, liverspecific expression in transgenic mice.Genes Devel. 1, 268–76.
Prophet, E.B., Mills, B., Arrington, J.B. and Sobin, L.H. (1992)Laboratory Methods in Histotechnology. Armed Forces Institute of Pathology, pp. 177. Washington, DC: American Registry of Pathology Pub.
Pursel, V.G., Pinkert, C.A., Miller, K.F., Bolt, D.J., Campbell, R.G., Palmiter, R.D., Brinster, R.L. and Hammer, R.E. (1989) Genetic engineering of livestock.Science 244, 1281–7.
Quaife, C.J., Mathews, L.S., Pinkert, C.A., Hammer, R.E., Brinster, R.L. and Palmiter, R.D. (1989) Histopathology associated with elevated levels of growth hormone and insulin-like growth factor 1 in transgenic mice.Endocrinology 124, 40–8.
Short, M.K., Clouthier, D.E., Schaefer, I.M., Hammer, R.E., Magnuson, M.A. and Beale, E.G. (1992) Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice.Mol. Cell. Biol. 12, 1007–20.
Steger, R.W., Bartke, A. and Cecim, M. (1993) Premature ageing in transgenic mice expressing different growth hormone genes.J. Reprod. Fertil. Suppl.46, 61–75.
Striker, L.J., Doi, T., Striker, G.E. (1991) Transgenic mice in renal research.Advances in Nephrology 20, 91–108.
Verstegen, M.W.A., van der Hel, W., Brandsma, H.A., Henken, A.M., Kanis, E. and van der Wal, P. (1991) Effects of recombinant procine somatotropin on metabolic rate in growing pigs.J. Anim. Sci. 69, 2961–70.
Wieghart, M., Hoover, J.L., McGrane, M.M., Hanson, R.W., Rottman, F.M., Holtzman, S.H., Wagner, T.E. and Pinkert, C.A. (1990) Production of transgenic pigs harbouring a rat phosphoenolpyruvate carboxykinase-bovine growth hormone fusion gene.J. Reprod. Fertil. Suppl.41, 89–96.
Yang, C.W., Striker, L.J., Pesce, C., Chen, W.Y., Peten, E.P., Elliot, S., Doi, T., Kopchick, J.J. and Striker, G.E. (1993) Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone.Lab. Invest. 68, 62–70.