The murine myostatin mutation Mstn(Cmpt-dl1Abc) (Compact; C) was introduced into an inbred mouse line with extreme growth (DUHi) by marker-assisted introgression. To study the allelic effects on muscle fibre hyperplasia and hypertrophy, myonuclear proliferation, protein accretion, capillary density, and muscle fibre metabolism, samples from M. rectus femoris (RF) and M. longissimus dorsi (LD) muscles of animals wild-type (+/+), heterozygous (C/+), and homozygous (C/C) for the Mstn(Cmpt-dl1Abc) allele were examined by histological and biochemical analyses. Homozygous C/C mice exhibited lower body (-12%) but higher muscle weights (+38%) than ++ mice. Total muscle fibre number was increased (+24%), whereas fibre size was not significantly affected. Protein and DNA concentrations and DNA:protein ratios as well as specific CK activity remained unchanged for higher mass muscle implying increases in the total contents of DNA and muscle specific protein. Fibre type distribution was markedly shifted to the white glycolytic muscle fibres (+16-17% units) at the expense of red oxidative fibres. Capillary density was substantially lower in C/C than in ++ mice as seen by lower number of capillaries per fibre (-35%) and larger fibre area per capillary (+77%). However, the Mstn(Cmpt-dl1Abc) allele was partially recessive in heterozygous C/+ mice for both fibre type frequencies and capillary density. The results show that hypermuscularity caused by mutations in the myostatin gene results from muscle fibre hyperplasia rather than hypertrophy, and from balanced increases in myonuclear proliferation and protein accretion. However, capillary supply is adversely affected and muscle metabolism shifted towards glycolysis, which could have negative consequences for physical fitness.

Myostatin is a negative regulator of muscle growth and mutations in its gene lead to muscular hypertrophy and reduced fat. In cattle, this is seen in 'double muscled' breeds. We have used marker-assisted introgression to introduce a murine myostatin mutation, MstnCmpt-dl1Abc [Compact (C)], into an inbred line of mice (DUHi) that had been selected on body weight and had exceptional growth. Compared with homozygous wild-type mice, homozygous (C/C) mice of this line were approximately 4-5 % lighter, had approximately 7-8 % shorter tails, substantially increased muscle weights (e.g. quadriceps muscle in males was 59 % heavier) and an increased 'dressing percentage' (approximately 49 % vs 39 %), an indicator of overall muscularity. The weights of several organs (e.g. liver, kidney, heart and digestive tract) were significantly reduced, by 12-20 %. Myostatin deficiency also resulted in drastic reductions of total body fat and of various fat depots, total body fat proportion falling from approximately 17.5 % in wild-type animals of both sexes to 9.5 % and 11.6% in homozygous (C/C) females and males, respectively. Males with a deficiency in myostatin had higher gains in muscle traits than females. Additionally, there was a strong distortion of the segregation ratio on the DUHi background. Of 838 genotyped pups from inter se matings 29 %, 63 % and 8 % were homozygous wild type (+/+), heterozygous (C/+) and homozygous (C/C), respectively, showing that MstnCmpt-dl1Abc has lower fitness on this background. This line, when congenic, will be a useful resource in gene expression studies and for finding modifying genes.

Mouse lines long-term selected for high fatness offer the possibility to identify individual genes involved in the development of obesity. The Berlin Fat Mouse (BFM) line has been selected for low protein content and afterward for high fatness. Three Berlin Fat Mouse Inbred (BFMI) lines, which are derivates of the selection line BFM and an unselected control line (C57BL/6; B6) were systematically phenotyped between 3 and 20 wk. The body weights and body compositions were measured on a weekly basis. We demonstrated that the BFMI lines dispose of more body weight, body fat mass, and body lean mass than the control line B6 because of a better feed efficiency in these lines. In contrast to other growth-selected mouse lines, the BFMI lines exhibited a general increase in body fat mass but only a marginal increase in body lean mass. The three BFMI lines also showed line- and sex-specific patterns and varied in their response to high-fat diet. The phenotypic differences between the BFMI lines can be traced back to different sets of fixed alleles contributing to fat accumulation and diet-induced obesity. Our results demonstrate that the genetically related BFMI lines are novel models to study the genetic as well as the nutritional aspects of obesity.

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.

Abstract. Eight beef cattle breeds, Angus (A), Blonde d' Aquitaine (BA), Charolais (C), Czech Pied (CP), Hereford (H), Limousin (L), Piemontese (P) and Simmental (S), were analysed for the following calf traits: birth weight (BW), 210- and 365-day weight ( 210W, 365W) and average daily gains from birth to 210 days (ADG1), from 210 to 365 days (ADG2) and from birth to 365 days (ADG3). Phenotypic parameters were estimated by linear model procedures including the fixed effects of year of birth (1992–1998), herd, sex (male, female), calf number (single, twin), parity and random sire effects. Literature values of heritability estimates were used to derive genetic standard deviations and genetic range for comparison of genetic variation within and between breeds. The means of Blonde d' Aquitaine were highest for all growth traits except for BW, followed by Charolais and Simmental, then Angus, Czech Pied and Limousin with intermediate values and Piemontese and Hereford with lowest growth except for BW in Piemontese and ADG1 in Hereford. Blonde d' Aquitaine also showed high standard deviations for most growth traits except for BW, whereas for Limousin and Piemontese low standard deviations were estimated and for other breeds no consistent pattern was observed. Coefficients of variation were generally high for Hereford and low for Angus. Hypothetical frequency curves were used for comparison of genetic variation within breeds and between breeds. Comparison of extreme and average breeds showed ranges of genetic levels between 79 and 154 % of the average breed level thus indicating the large overall genetic variation for growth traits in beef cattle. Between-breed selection with immediate impact, but steady erosion by time, as well as within-breed selection with slow but steady increase and renewed variation should both be applied for optimal exploitation of genetic resources in the beef industry.