Abstract
BackgroundCataracts 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 acquired (age-related) lesions.ResultsHere 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. This 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.S229N) in the C-terminal tail of the protein, and modeling predicts that the mutation induces conformational changes that may interfere with lens permeability and cell–cell interactions.ConclusionThe c.686G > A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.
Highlights
Cataracts are defects of the lens that cause progressive visual impairment and blindness in many vertebrate species
We identified and characterized a novel missense mutation in the major intrinsic protein (MIP) gene of a female panda diagnosed with progressive cortical punctate cataracts
Jini’s mild cataract symptoms were first observed in 2013, and in 2017 the lesion was diagnosed as a unilateral senile cataract following a professional examination by an ophthalmologist (Fig. 1)
Summary
Cataracts are defects of the lens that cause progressive visual impairment and blindness in many vertebrate species. Whereas some congenital cataracts are caused by the disruption of eye development, others reflect the presence of mutations in genes required for normal lens function [2]. Several mutations have been traced to genes encoding crystallin proteins, which normally remain soluble and confer transparency, including α-crystallins [10], β-crystallins [11,12,13], and γ-crystallins [14, 15]. Another major category of cataract-promoting mutations affect genes encoding lens membrane channels or gap junction proteins, such as connexin 46 (GJA3) [16] and connexin 50 (GJA8) [17]. One of the most important membrane channels in the context of cataract formation is the lens major intrinsic protein (MIP), known as aquaporin 0 (AQP0) [18]
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