Marker-assisted introgression of the Compact mutant myostatin allele MstnCmpt-dl1Abc into a mouse line with extreme growth effects on body composition and muscularity
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 ~4–5% lighter, had ~7–8% shorter tails, substantially increased muscle weights (e.g. quadriceps muscle in males was 59% heavier) and an increased ‘dressing percentage’ (~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 ~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.(Received January 12 2004)
(Revised April 17 2004)
(Revised August 30 2004)
c1 Scottish Agricultural College, SLS, GGS, Sir Stephen Watson Building, Bush Estate, Penicuik, Midlothian, EH26 0PH, UK. Tel: +44 (0)131 535 3227. Fax: +44 (0)131 535 3121. e-mail: L.Bunger@ed.sac.ac.uk
p1 Current address: Scottish Agricultural College, SLS, GGS, Sir Stephen Watson Building, Bush Estate, Penicuik, Midlothian, EH26 0PH, UK.