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Parks, Elizabeth ; Striker, Liliane J. ; Striker, Gary E. ; Kopchick, John J.
Komitet Biotechnologii PAN ; Instytut Chemii Bioorganicznej PAN
Transgenic mice which overexpress growth hormone (GH) may be used a model system toexamine growth, kidney pathology, as well as the medical condition known as acromegaly (hyper-growth hormone secretion). GH is a pleiotropic 22 kDa polypeptide hormone which elicitsbody growth in jeuvenille animals and also mediates protein, carbohydrate, and lipid metabolism.The structure/function relationships of selected residues of bovine (b) GH a-helix I were approached using site-directed mutagenesis in concert with the production of bGH analog transgenicmice. Phenyalanine (Phe, F) 11 and histidine (His, H) 22 in the amino-terminus of bGH werethe targeted amino acids. bGH and the bGH analog transgenic mice all exhibited the enhancedgrowth phenotype similar to bGH transgenic mice and had elevated IGF-1 serum concentrations.However, bGH-H22R mice demonstrated levels of blood urea nitrogen (BUN) and serum creatinine(SCR) several fold higher than the other transgenic mice. Elevated BUN and SCR are an indicationof renal insufficiency in this mouse line. Glucose tolerance testing in the bGH-H22R mice revealedthat they possessed a lower tolerance for glucose, or an enhancement of the diabetogenic properties of the hormone as compared to wild-type and other GH analog transgenic mice: Inaddition to the glomerulosclerosis found in bGH mice, histological examination of the maturebGH-H22R mice demonstrated severe glomerulosclerosis, as well as cystic kidney lesions.
Biotechnologia, vol.41, 2 (1998)-.
0860-7796 ; oai:rcin.org.pl:144342 ; IChB B-37
Biblioteka Instytutu Chemii Bioorganicznej PAN
Licencja Creative Commons Uznanie autorstwa-Na tych samych warunkach 4.0
Instytut Chemii Bioorganicznej Polskiej Akademii Nauk
Instytut Chemii Bioorganicznej Polskiej Akademii Nauk
18 lis 2020
26 paź 2020
57
https://rcin.org.pl./publication/179687
Nazwa wydania | Data |
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Alteration in bovine growth hormone histidine 22 results in transgenic mice with an enhanced diabetogenic profile | 18 lis 2020 |
Borkowska, Bożenna
Ziółkowski, Piotr Babula- Skowrońska, Danuta Kaczmarek, Małgorzata Cieśla, Agata Sadowski, Jan
Nowak, Jacek K.
Kopchick, John J. Jura, Jacek Mukerji, Pradip Kelder, Bruce
Jura, Jacek Smorąg, Zdzisław Gajda, Barbara Kareta, Wiesław Kopchick, John J. Kelder, Bruce Prieto, Pedro A.