Inger Anne Boman defended her PhD thesis on June 29th 2009

Ane Gro Siri Skjelfjord

**Mutations in the myostatin (MSTN) gene in Norwegian sheep**

Two mutations in the myostatin gene (MSTN) were identified in Norwegian sheep. These are a deletion of a single guanine (G) base in cDNA position 960 (c.960deIG), and an insertion of the single adenine (A) base in cDNA position 120 (c. 120insA). In addition, a 3' -UTR mutation creating an illegitimate microRNA site (c.2360G>A) that was identified in Texel sheep by Clop and coworkers, was also discovered to segregate in Norwegian sheep. While the occurrence of c.960delG was restricted to Norwegian White Sheep (NWS), the c.120insA mutation was only found in Norwegian Spælsau. The c.2360G>A was present in both breeds - but at a much higher frequency in NWS than in Spælsau. No animals homozygous for one of the mutations have carried a second mutation, which indicates that they reside in different haplotypes.

The c.120insA causes a disrupted reading frame including amino acid (aa) position 40 and onwards, ending in a premature stop codon in aa position 49. The c.960delG causes a disrupted reading frame including aa position 320 and onwards, ending in a premature stop codon in aa position 359. Since the functional part of the protein constitute of aa residues 267-375, the homozygous c.120insA and c.960delG individuals do not produce a functional MSTN protein. Animals homozygous for the c.2360G>A mutation are reported to have approximately one-third of normal level of circulating myostatin protein.

The effect of c.960delG and c.2360G>A was investigated through a field experiment with NWS. Both mutations reduced fatness and increased muscle mass in lamb carcasses, though the effect of the frameshift mutation (c.960deIG) was more profound compared to the 3'-UTR mutation (c.2360G>A). Lambs homozygous for the c.960delG mutation grew slower than the other MSTN genotypes and had a reduced survival rate, but had least fat and the largest muscle mass. Lambs heterozygous for both c.960delG and c.2360G>A (compound heterozygote) had a higher rate of birth assistance, which is consistent with a significantly increased birth weight for this group. Thus, the two genotype classes yielding most increased muscle mass and least fat are associated with unwanted side effects. Genotype class had no statistically significant effect for any of the fertility traits.

The Norwegian Sheep Breeding Council decided in 2008 to genotype all rams for the MSTN mutations before final approval for AI, and to remove all rams carrying the mutations c.120insA or c.960deIG. The decision was based upon the results from this study.

The frequency of the c.2360G>A mutation has increased significantly among the NWS AI rams since 1990. It is suggested that the introduction of BLUP animal model indexes in 1991 and EUROP carcass classification in 1996 have been important drivers in this development. Most likely c.2360G>A will be brought to fixation within a few additional generations, if the current selection pressure is maintained.
Keywords: GDF8, increased muscle mass, MSTN, myostatin, sheep, fertility, survival

Aderess as of July 2009: The Norwegian Association of Sheep and Goat Farmers (NSG), c/o UMB, IHA, Postboks 5003, 1432 Ås

Updated: 01.07.09
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