Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast growth factor receptor 31

Abstract

Normal fibroblast growth factor receptor 3 (FGFR3) acts as a negative bone growth regulator by restricting chondrocyte proliferation and endochondral bone elongation. In sheep, a heritable mutation that inactivates FGFR3 produces skeletal overgrowth when homozygous, this condition is commonly referred to as spider lamb syndrome (SLS). We hypothesized that sheep heterozygous for the inactivated FGFR3 mutation (FGFR3(SLS/+)) would exhibit enhanced long bone growth and greater frame size; additionally, the isolated effects of increased bone growth would translate into greater BW and larger LM area relative to normal lambs at harvest. The current study investigated bone length and LM area of FGFR3(SLS/+) sheep at maturity and during growth. At maturity, FGFR3(SLS/+) ewes exhibited a larger frame size and longer bones than normal FGFR3(+/+) ewes (P < 0.05). Similarly, FGFR3(SLS/+) lambs had greater frame sizes than normal FGFR3(+/+) lambs, as indicated by increased metacarpal III length and height at withers (P < 0.05). The FGFR3(SLS/+) lambs took longer than the normal FGFR3(+/+) lambs to reach the 60-kg common BW harvest end point (P < 0.05). The FGFR3(SLS/+) lambs showed no difference in BW, ADG, or LM area at any age compared with normal FGFR3(+/+) lambs (P > 0.2). A similar LM area produced in the context of a greater frame size and skeletal length produces a greater muscle volume, thereby potentially increasing meat yield. The results of this study suggest that FGFR3(SLS/+) animals exhibit a relaxation of the normal inhibition of chondrocyte proliferation, resulting in an increase in the overall frame size. The sheep industry could utilize the naturally occurring genetic mutation in FGFR3 to potentially increase meat yields with enhanced skeletal growth as an alternative to exogenous growth promotants.