Males are at greater risks of obstruction due to urinary calculi than females, because of smaller urethras [89] so that stones pass less easily. that meat from double-muscled animals is mostly more tender. However, meat tenderness, color and juiciness are not always improved. A different metabolism as a consequence of faster glycolytic myofibers can be partly Hsp25 responsible for this phenomenon. DM animals are interesting for the producer and butcher, and beneficial for the consumer, if an appropriate nutrition and accommodation, and adequate slaughter conditions are taken into account. Abstract Molecular biology has enabled the identification of the mechanisms whereby inactive myostatin increases skeletal muscle growth in double-muscled (DM) animals. Myostatin is a secreted growth differentiation factor belonging to the transforming growth factor- superfamily. Mutations make the myostatin gene inactive, resulting in muscle hypertrophy. The relationship between the different characteristics of DM cattle are defined with possible consequences for livestock husbandry. The extremely high carcass yield of DM animals coincides with a reduction in the size of most vital organs. As a consequence, DM animals may be more susceptible to respiratory disease, urolithiasis, lameness, nutritional stress, heat stress and dystocia, resulting in a lower robustness. Their feed intake capacity is reduced, necessitating a diet with a greater nutrient density. The modified myofiber type is responsible for a lower capillary density, and it induces a more glycolytic metabolism. There are associated changes for the living animal and post-mortem metabolism alterations, requiring appropriate slaughter conditions to maintain a high meat quality. Intramuscular fat content is low, and it is characterized by more unsaturated fatty acids, providing healthier meat for the consumer. It may not always be easy to find a balance between the different disciplines underlying the livestock husbandry of DM animals to realize a good performance and health and meat quality. muscle in response to an 11-bp deletion in the MSTN gene showed that thirteen proteins are significantly altered between BBDM and non-DM animal muscles. Eight proteins are related to the contractile apparatus, two proteins are involved in metabolic pathways, and three proteins are significantly altered including sarcosin, sarcoplasmic reticulum 53 kDa glycoprotein and 20 kDa heat shock protein [27]. McPherron and Lee [17] also sequenced the MSTN gene in the Piedmontese breed. The similar map positions of the MSTN gene and the muscular hypertrophy locus and the identification of relatively severe mutations in the MSTN gene of two different DM cattle breeds suggest that these mutations are responsible for the DM phenotype. Mutations in Belgian Blue and Piedmontese DM cattle are different [9]. The entire MSTN coding sequence in ten European cattle breeds was determined [28]. The observation that in at least eight of the ten studied breeds double muscling involves five independent MSTN mutations indicates that the number of genes susceptible to affect muscular development in a comparable way is likely BMS-790052 2HCl to be limited in cattle. The role of MSTN in the regulation of cell growth and cell death occurs in concert with insulin-like growth factor (IGF)-I [29]. It has been shown that the maximum expression of muscle IGF-II is delayed in DM animals during fetal development [30]. A differential regulation of the IGF-II gene transcription between DM and normal fetuses was also reported [31]. Insulin-like growth factor binding proteins (IGFBP-3 and IGFBP-5) affect processes downstream the receptor-mediated SMAD phosphorylation, enabling MSTN to suppress proliferation of porcine embryonic myogenic cells [32]. The role of IGF and IGFBP was also confirmed in mice [33]. MSTN null mice have higher circulating IGF-I levels than wild-type mice, whereas IGFBP-1 and IGFBP-2 levels were lower. Furthermore, it is assumed that the relative IGF-binding capacity was potentially lower BMS-790052 2HCl in MSTN null mice. Muscle regulatory factors (MRF4, Myf5, MyoD and myogenin) play a key role in muscle development and maturation [34,35]. A distinct pivotal function in muscle development is attributed to each of these muscle regulatory factors. The expression of MyoD BMS-790052 2HCl in fetal bovine muscles is up-regulated by the loss of functional MSTN [36,37,38]. Higher levels of MyoD expression throughout primary and secondary fiber formation were found in BBDM fetuses compared to non-DM fetuses [37,38]. Higher expressions of MRF4, Myf5 and MyoD were found in DM than in non-DM Japanese Shorthorn cattle, but the effect was different between muscles [39]. Furthermore, the effect of MSTN on MRF4 expression may be more specific for fast type muscle fibers. Myf5 and MyoD expressions were increased in faster and slower.