Subtitle:

Alteration in bovine growth hormone histidine 22 results in transgenic mice with an enhanced diabetogenic profile

Publisher:

Committee on Biotechnology PAS ; Institute of Bioorganic Chemistry PAS

Abstract:

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.

Relation:

Biotechnologia, vol.41, 2 (1998)-.

Volume:

41

Issue:

2

Start page:

161

End page:

173

Detailed Resource Type:

Article

Format:

application/pdf

Resource Identifier:

0860-7796 ; oai:rcin.org.pl:144342 ; IChB B-37

Source:

Library of Institute of Bioorganic Chemistry PAS

Language:

pol

Language of abstract:

eng

Temporal coverage:

1988-2010

Rights:

Creative Commons Attribution BY-SA 4.0 license

Terms of use:

Copyright-protected material. [CC BY-SA 4.0] May be used within the scope specified in Creative Commons Attribution BY-SA 4.0 license, full text available at:

Digitizing institution:

Institute of Bioorganic Chemistry of the Polish Academy of Science

Original in:

Institute of Bioorganic Chemistry of the Polish Academy of Science

Projects co-financed by:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Access:

Open