In livestock production, there is a high interest in controlling meat quantity and quality; knowledge about genes affecting muscle size and other meat properties can help breeders to select animals according to desired traits. Myostatin (Mstn, or growth and differentiation factor 8 - Gdf8) was first identified in knock-out mice as being a gene responsible for regulation of muscle growth . However, the hypermuscular phenotype that originates from a hyperplasia and hypertrophy of muscle fibres was known long before its molecular-genetic background was elucidated . In sheep, pigs and cattle, several mutations of myostatin or its promoter region have been identified as affecting muscle size [3–6]. Furthermore, myostatin also influences glucose metabolism and fat accumulation, as shown in knock-out mice that had smaller adipocytes  and did not develop obesity on a high-fat diet. These results suggested an altered metabolism for the utilization of lipids and glucose as energy fuel that prevented insulin resistance in mice [8, 9]. A decreasing effect on intramuscular fat (IMF) content and carcass fat proportion was also described for the “double-muscled” phenotypes in cattle [10, 11], which was later found to be caused by a myostatin mutation as well. However, different myostatin mutations can cause different degrees of hypermuscularity. The most extreme form of this phenotype in cattle is seen in the Belgian Blue, while different mutations with less extreme phenotypes were identified in other breeds .
Due to its large implication, not only on skeletal muscles, a lot of research has been undertaken on the effects of myostatin and its possible applications in health care and livestock production. The myostatin-gene, for instance, appears to be a promising candidate for the treatment of muscle dystrophy diseases [13, 14], cardiac tissue regeneration or metabolic syndrome [15, 16]. In livestock, efforts to manipulate the gene’s expression through immunization have been made for the purposes of higher lean mass production . In accordance with this, modifiers of myostatin, such as follistatin (Fst), which inhibits myostatin, are currently under review as therapeutics [18, 19].
In the present study, we generated G3-populations of reciprocal crosses between two hypermuscular Berlin Muscle Mouse Inbred (BMMI) lines to examine the genetic characteristics of myostatin and to find additional genes that could influence muscle growth and composition. The BMMI lines were hypermuscular as a result of long term selection that mirrors the selection process for high meat yield in livestock. The parental BMMI866 line originates from a population with the “compact” phenotype and therefore carries the known Mstn
mutation [20, 21]. Although the BMMI806 line originates from the same founder population, it does not carry this mutation; BMMI806 animals display very high intramuscular fat contents, fat mass and fat proportion, especially in males . Previously, genetic modifier regions for the effect of the myostatin Mstn
mutation on muscle mass have been identified on chromosomes 3, 5, 7, 11, 16, and X in a cross between Comp9 and CAST/Ei lines .
Given that the BMMI lines were originally developed as supporting genetic models for livestock research, we were particularly interested in myostatin effects on intramuscular fat content (IMF) and water holding capacity (WHC) on the genetic background of high muscularity. We also analysed the extent to which sex and the direction of the reciprocal cross impacted on the traits of interest. The latter could indicate parent-of-origin effects, where the impact on the phenotype can be different depending on the parent from which an allele was inherited. For example, the polar over-dominance caused by the ovine callipyge locus, where a hypermuscular phenotype only occurs if the mutated allele is inherited from the sire [24, 25]. Parent-of-origin effects have also been described for body composition and fat-related traits in mice, pigs and cattle [26–29].
In addition to the relationship between muscle mass and meat quality traits, we were also interested in certain parameters of the muscle and whole body metabolism such as muscle glycogen and lactate contents, blood glucose levels, and the carcass pH-values. For this purpose, we present the correlations between these traits in the G3-population. The linkage study did not reveal genomic loci accounting for variation of those metabolic traits.