Inbred lines of mice derived from long-term growth selected lines: unique resources for mapping growth genes

Abstract

Lines of mice selected for many generations for high or low growth in several laboratories around the world have been collected, and from these, inbred lines are being developed by recurrent full-sib mating in Edinburgh. There are seven high selected lines and four low lines (each low line is from the same base population as one of the high lines), and the histories of each are summarized. Mean body weight of males at 70 days of age in the Edinburgh laboratory in the heaviest inbred line (77 g) is 4.8-fold higher than in the lightest line (16 g), and 1.9-fold higher than in the least extreme high line (41 g). Litter size, food intake, and fat content also differ substantially. These inbred extreme selected lines are a uniquely valuable resource for QTL or gene mapping, candidate gene identification, and elucidation of epistatic effects.

Lack of myostatin results in excessive muscle growth but impaired force generation

“…Additionally, mice from a subline of the BEH have been used (35). The BEH line is homozygous for the compact mutation (36) and is coded as Mstn ComptϪdl1ABC (37,38).…”

“…The BEH line is homozygous for the compact mutation (36) and is coded as Mstn ComptϪdl1ABC (37,38). Mice from the BEH line were crossed with mice from the Berlin Low line (BEL) to introduce the wild type back into the BEH mice, to allow segregation of the wild-type and the compact allele in this subline, coded BEH C/ϩ (35). Heterozygous mice from BEH C/ϩ have been repeatedly backcrossed to mice from the BEH line to reestablish the high growth background of this line, which had been long-term selected for high growth (35).…”

“…Mice from the BEH line were crossed with mice from the Berlin Low line (BEL) to introduce the wild type back into the BEH mice, to allow segregation of the wild-type and the compact allele in this subline, coded BEH C/ϩ (35). Heterozygous mice from BEH C/ϩ have been repeatedly backcrossed to mice from the BEH line to reestablish the high growth background of this line, which had been long-term selected for high growth (35). The mice used here were sampled after completion of five backcross generations (including F 1 ), which had on average 98.44% of genetic background of the BEH line reestablished.…”

Genetic architecture of body size in mammals

“…(a) Angus cattle [35] and (b) mice [36] from long-term selection experiments for high and low growth show phenotypes outside the normal range of the unselected population. The photographs were kindly supplied by Robert Herd (NSW Department of Primary Industries, NSW, Australia) and Lutz Bünger (University of Edinburgh, Edinburgh, UK).…”

Inbred mouse strains and genetic stability: a review

“…The little mutation, an Asp to Gly substitution in the growth hormone-releasing hormone receptor gene (Lin et al, 1993), spontaneously arose in the C57BL/6J inbred colony from the Jackson Laboratory (Eicher and Beamer, 1976), and originated one of the first dwarf animal models along with the Snell (Li et al, 1990) and Ames (Brown-Borg et al, 1996) dwarf mutations. The same phenomenon arose in a synthetic outbred population originating from a four-way experimental cross (AKR/ J 3 C3H 3 C57BL/6J 3 DBA/2; Bradford, 1971;Bü nger et al, 2001) in the University of California (Davis, CA, USA), although the phenotypic output relied on the opposite effect. Mutant mice suffered 30% to 50% postweaning overgrowth due to a spontaneous 500-kb deletion involving the Socs2 gene (Horvat and Medrano, 2001;Wong et al, 2002).…”