Role of growth hormone in the genetic change of mice divergently selected for body weight and fatness

Abstract

To elucidate the involvement of growth hormone (GH) in the genetic change produced by long-term selection in growth and fatness, a ‘GH knock-out study’ on over 900 mice was undertaken. Lines used had been selected for more than 50 generations for high (PH) and low (PL) body weight (initially protein mass) at 70 d(ays) and for high (F) and low fat content (L) at 98 d, producing a 3-fold difference in body weight and a 5-fold difference in fat content. GH deficiency was achieved by repeated backcrossing into each line a recessive mutant gene (lit) which has a defective GH releasing factor receptor. In the absence of GH, the P lines still differ in body weight (21 d to 98 d): e.g. at 98 d homozygous lit/lit: PH = 24·2 g, PL = 10·0 g; wild-type (wt): PH = 57·4 g, PL = 18·7 g. The effect of the GH deficiency on body weight (untransformed) was very much larger in the PH than in the PL line, but the interaction was much smaller, although still significant, on the log scale. This indicates that changes in the GH system contribute only a small part of the selection response in growth. GH deficiency increased fat percentage in all lines (including P), especially in males (99 d, males lit/lit: F = 26·4%, L = 6·9%; wt: F = 22·0%, L = 4·8%; females: 20·2%, 5·2%, 20·7%, 3·0%) with significant genotype×line and genotype×sex interactions. The interactions between the effects of the lit gene and the genetic background were, however, relatively small compared with these main effects and again indicate that other systems contributed most of the selection response.