Harmonin in the murine retina and the retinal phenotypes of USH1C-mutant mice and human USH1C.

摘要: Usher syndrome is an inherited deafness–blindness disorder, characterized by both cochlear dysfunction and progressive retinal degeneration (retinitis pigmentosa). It has been divided into three general clinical subtypes, Usher-1, -2, -3, but it can be caused mutations in any one of 11 different genes. type 1C the gene, USH1C, which encodes for a PDZ-domain protein, referred to as harmonin.1 Harmonin was originally identified antigen autoantibodies generated patients with colon cancer2 present wide range tissues.3 Harmonin expressed alternatively spliced isoforms that make up different-sized subclasses.1 Because its PDZ-domains, harmonin proposed function scaffolding protein.1 In support, vitro binding studies have shown all other known Usher-1 proteins, myosin VIIa, cadherin23, protocadherin15, SANS, bind PDZ domains harmonin,4–6 do two 2 usherin, VLGR1.7 As consequence, -2 proteins large interactive complex core.7–10 This unifying hypothesis attractive may simplify loss-of-function group otherwise very apparent functions. However, our understanding situ most insufficient test this adequately. lack especially true respect retina. In study, we focused on increasing retina. We re-evaluated expression retina, studied retina Ush1c mutant mouse, performed structural functional analyses retinas sibship USH1C mutations.