Identification of the Gene Responsible for Chicken Muscular Dystrophy

Abstract

By a series of positional cloning, we successfully narrowed down the AM candidate region to approximately 1.2 Mbp on GGA2q including 7 functional genes. Subsequently, we identified WWP1 gene as the most likely AM candidate by sequence comparison. The amino acid sequence around the candidate mutation was highly conserved among tetrapods, suggesting that WWP1 is the causative gene of chicken muscular dystrophy. Transfection of mutated WWP1 gene into C2C12 myoblasts disrupted muscle differentiation process. The abnormal muscle differentiation is a characteristic of chicken muscular dystrophy, so we could demonstrate a part of phenotype of the disease. Furthermore, western blotting revealed that accumulation of caveolin-3 protein is limited in damaged muscle of muscular dystrophic chicken, suggesting caveolin-3 may be associated with the pathological change of the disease. We could conclude that WWP1 gene is the responsible one for chicken muscular dystrophy from these results, but the mechanism leading the onset should be clarified in the future. The information will contribute to the study of chicken muscular dystrophy and the corresponding human dystrophies.

Caveolin-3: A Causative Process of Chicken Muscular Dystrophy

“…The sequence comparison and analysis of seven genes in normal and dystrophic chickens revealed that the WWP1 missense mutation was predicted to influence the function of the WWP1 protein. The WWP1 missense mutation was not found in 111 normal birds from 16 strains and highly conserved among tetrapods [ 21 , 59 ].…”

Characterization of Insertional Variation of Porcine Endogenous Retroviruses in Six Different Pig Breeds

“…Livestock species have been widely used for the biomedical researches, especially for chickens and pigs ( Matsumoto et al, 2011 ; Robb et al, 2011 ; Luo et al, 2012 ). Xenotransplantation using porcine cells, tissues and organs has focused on biomedical aspects, with the aim of decreasing wait times for patients who require an allotransplantation.…”