Submitted to: Transgenic Animal Research Conference
Publication Type: Abstract Only
Publication Acceptance Date: 8/2/2009
Publication Date: 8/20/2009
Citation: Yang, J., Schulman, L., Pursel, V.G., Solomon, M.B., Mitchell, A.D., Zhao, B., Li, Z., Wall, R.J. 2009. Expression of porcine myostatin prodomain genomic sequence leads to a decrease in muscle growth, but significant intramuscular fat accretion in transgenic pigs. Transgenic Animal Research Conference VIII, p. 15. Interpretive Summary: n/a
Technical Abstract: Myostatin, a member of TGF-beta superfamily, is a dominant inhibitor of skeletal muscle development and growth. Previously, skeletal muscle-specific over-expression of myostatin prodomain cDNA (5’-region 886 nucleotide) dramatically increased growth performance and muscle mass in transgenic mice. In an attempt to apply the same strategy of down-regulating myostatin activity in pig skeletal muscle, transgenic pigs were generated by pronuclear microinjection of a transgene consisting of myosin light chain 1 promoter and porcine myostatin prodomain genomic sequence. Four transgenic founder pigs out of 77 live piglets born were identified by Southern blots. One transgenic founder expressed the expected 0.9 kb transgene and two other transcripts (2.9 kb and 1.5 kb) which hybridized with the prodomain probe during Northern blot analysis. Growth and carcass composition of the transgenic pigs were compared in the second generation with non-transgenic littermate controls. The number of days to reach 120 kg liveweight was higher in transgenic pigs than their littermate (214.5 ' 4.6 vs 195.4 ' 3.3, P=0.002). Individual muscle weights of biceps femoris, semitendinosis, rectus femoris, psoas major, triceps brachii and semimembrinosis were all lower in transgenic pigs than their littermate controls (P<0.05) at 120-kg slaughter weight. Percentages of body fat measured by Dexa analysis were also higher (P<0.05) in transgenic pigs than their littermate controls at 60, 90 and 120 kg liveweight. Interestingly, the transgenic pigs had significantly higher content of intramuscular fat in the longissimus dorsi compared with non-transgenic pigs (30-40% vs 3-8%). A large number of adipocytes were present in biopsied muscle in gilts and barrows at 60 kg and 120 kg liveweight. More than 50% of the transgenic pigs at 60 kg and 120 kg liveweight also showed atypical succinic dehydrogenase/ATPase stain reactions, macrophage activity and necrotic phagocytosis as a result of increased fat accumulation in the muscle. The phenotypes of the transgenic pigs suggest an up-regulated myostatin function instead of depressed myostatin activity, which may result from inappropriately splicing the genomic sequences of the transgene construct.