title: Segregation ratios and growth rate in inactive ovine metallothionein 1a-ovine growth hormone transgenic mice.
abstract: Objectives were to determine whether the oMt1a-oGH transgene shows normal Mendelian segregation and whether oMt1a-oGH mice exhibit normal growth without the zinc supplementation required to increase plasma oGH levels and stimulate growth. Transgenic mice were reciprocally backcrossed for four generations to high growth and control lines to form lines GM and GR, respectively. In the fifth generation, hemizygous transgenic mice (T/-) were crossed within 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/- x T/- cross, the combined percentage of homozygous (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 relative 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 back-cross 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 survival. Reduced growth of oMt1a-oGH transgenic mice when the transgene is switched off suggests a subtle developmental abnormality, which may contribute to a reduction in fitness.
authors.affiliation: Department of Animal Science, North Carolina State University, Raleigh 27695, USA. gene_eisen@ncsu.edu
authors.forename: E J
authors.initials: EJ
authors.lastname: Eisen
authors.forename: J D
authors.initials: JD
authors.lastname: Murray
mesh_terms: D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000235:genetics*; D006720:Homozygote; D016018:Least-Squares Analysis; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000254:growth & development*; D012756:Sheep; D019076:Transgenes; D015032:Zinc / Q000494:pharmacology
chemical_list: D013006:Growth Hormone; D008668:Metallothionein; D015032:Zinc