title: Marker-assisted introgression of the Compact mutant myostatin allele MstnCmpt-dl1Abc into a mouse line with extreme growth effects on body composition and muscularity.
abstract: 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.
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JT, UK. L.Bunger@ed.sac.ac.uk
authors.forename: Lutz
authors.initials: L
authors.lastname: Bünger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ott
authors.forename: László
authors.initials: L
authors.lastname: Varga
authors.forename: Werner
authors.initials: W
authors.lastname: Schlote
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rehfeldt
authors.forename: Ulla
authors.initials: U
authors.lastname: Renne
authors.forename: John L
authors.initials: JL
authors.lastname: Williams
authors.forename: William G
authors.initials: WG
authors.lastname: Hill
mesh_terms: D000483:Alleles; D000818:Animals; D015415:Biomarkers; D001823:Body Composition / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D005809:Genes, Regulator; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000254:growth & development*; D009929:Organ Size / Q000235:genetics; D013623:Tail / Q000033:anatomy & histology
chemical_list: D015415:Biomarkers