Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice.
AUTOR(ES)
Chen, W Y
RESUMO
To determine the importance of the third alpha-helix in bovine growth hormone (bGH) relative to growth-related biological activities, the following experimental approach was used: (i) mutagenesis of helix III of bGH to generate an idealized amphiphilic helix; (ii) in vitro expression analyses of the mutated bGH gene in cultured mouse L cells; (iii) mouse liver membrane binding studies of wild-type and mutated bGH; and (iv) expression of the mutated gene in the transgenic mouse. An altered bGH gene (pBGH10 delta 6-M8) was generated that encodes the following changes: glutamate-117 to leucine, glycine-119 to arginine, and alanine-122 to aspartate. The plasmid pBGH10 delta 6-M8 was shown to be expressed in, and its protein product secreted by, mouse L cells. The altered hormone possessed the same binding affinity to mouse liver membrane preparations as wild-type bGH. Transgenic mice containing the mutated bGH gene, however, showed a significant growth-suppressed phenotype. The degree of suppression was directly related to serum levels of the altered bGH molecule.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=54261Documentos Relacionados
- Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice.
- Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice.
- Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice.
- Expression of biologically active heterodimeric bovine follicle-stimulating hormone in milk of transgenic mice.
- Identification of rat growth hormone genomic sequences targeting pituitary expression in transgenic mice.