Spata7, a Homolog of the Human LCA3 Gene, Plays Key Roles in Mouse Retinal Development

Abstract

Purpose: : LCA is a set of inherited, early onset retinopathies that affect about 1 in 50,000 in the general U.S. population and accounts for more than 5% of all retinal dystrophies. We recently identified the causative gene associated with the LCA3 locus, named SPATA7, which encodes a highly conserved but novel protein of unknown function and for which no animal models have been established. Interestingly, SPATA7 mutations are associated with both LCA and retinitis pigmentosa (RP), suggesting that a detailed understanding of SPATA7 function could have broad implications for our ability to diagnose, prevent, and treat human retinal diseases. To characterize the function of SPATA7, we have generated homozygous null alleles of mouse Spata7.

Methods: : We have generated homozygous knock-out mice using Cre-LoxP system.

Results: : Consistent with the phenotype observed in human LCA patients, severe retinal defects are observed in Spata7 mutant mice. The total number of photoreceptor cells is dramatically reduced by four weeks of age. In addition, disorganization of both the inner and outer segments of photoreceptor cells is observed.

Conclusions: : Preliminary examination of several retinal markers also suggests potential defects in Rhodopsin localization, consistent with the idea that SPATA7 may play an essential role in protein transport. Further characterization of Spata7 in retinal development and function using both genetic and biochemical approaches will be reported.

Keywords: retina • development • mutations