Segregation ratios and growth rate in inactive ovine metallothionein 1a-ovine growth hormone transgenic mice

Objectives were to determine whether the oMt1a-oGH transgene shows normal M endelian segregation and whether oMtla-oGH mice exhibit normal growth witho ut the zinc supplementation required to increase plasma oGH levels and stim ulate growth. Transgenic mice were reciprocally backcrossed for four genera tions to high growth and control lines to form lines GM and GR, respectivel y. In the fifth generation, hemizygous transgenic mice (T/-) were crossed w ithin each line. Pooled across backcross generations, there was a deficit ( P < 0.001) of T/- progeny in lines GM (31.6%) and GR (22.2%) compared with expected (50%). In the T/- xT/- cross, the combined percentage of homozygou s (T/T) and hemizygous transgenic mice was less (P < 0.001) than expected ( 75%) in both GM (44.2%) and GR (38.5%). Backcross T/- mice had lower (P < 0 .05) 3-wk BW and lower (P < 0.001) 6-wk BW and 3-to 6-wk postweaning gains than nontransgenic mice. Similar genotypic differences were found in the T/ - x T/- cross. No significant growth differences were found between T/T and T/- progeny. Using segregation ratios from the T/- x T/- mating, the relat ive fitness estimates of T/T, T/-, and -/- (nontransgenic) mice were 0.345, 0.223, and 1.0, respectively, in line GM and 0.218, 0.205, and 1.0 in line GR. Fitness estimates in the backcross for T/- and -/- were 0.463 and 1.0 in line GM and 0.285 and 1.0 in line GR. Abnormal segregation ratios may be due to germline mosaicism or reduced fitness due to differential embryo su rvival. Reduced growth of oMt1a-oGH transgenic mice when the transgene is s witched off suggests a subtle developmental abnormality, which may contribu te to a reduction in fitness.