First Author | Chen WY | Year | 1990 |
Journal | Proc Natl Acad Sci U S A | Volume | 87 |
Issue | 13 | Pages | 5061-5 |
PubMed ID | 2367524 | Mgi Jnum | J:130459 |
Mgi Id | MGI:3771698 | Doi | 10.1073/pnas.87.13.5061 |
Citation | Chen WY, et al. (1990) Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci U S A 87(13):5061-5 |
abstractText | 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. |