A Novel Missense Mutation in the Gene Encoding Major Intrinsic Protein (MIP) in a Giant Panda with Cataracts
Abstract Background: Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or sporadic acquired (age-related) lesions. Results: Here we used a functional candidate gene- screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G>A) in the MIP gene encoding major intrinsic protein. , whichThis is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.229S>Np.S229N) in the C-terminal tail of the protein, and modeling revealed predicts that the mutation- induced induces conformational changes that may interfere with lens permeability and cell–cell interactions. Conclusion: The c.686G>A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions of in China, suggesting that c.686G>Ait is likely to bemost likely a genuine disease-causing associated mutation rather than a single-nucleotide polymorphism 5 regions was used in this research. Conclusions: The c.686G>A mutation was not found in healthy pandas, suggesting itThe mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.