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Brian P. Brooks, Denise M. Larson, Chi-Chao Chan, Sten Kjellstrom, Richard S. Smith, Mary A. Crawford, Lynn Lamoreux, Marjan Huizing, Richard Hess, Xiaodong Jiao, J. Fielding Hejtmancik, Arvydas Maminishkis, Simon W. M. John, Ronald Bush, William J. Pavan; Analysis of Ocular Hypopigmentation in Rab38 cht/cht Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(9):3905-3913. doi: 10.1167/iovs.06-1464.
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purpose. To characterize the ocular phenotype resulting from mutation of Rab38, a candidate gene for Hermansky-Pudlak syndrome.
methods. Chocolate mice (cht, Rab38 cht/cht ) and control heterozygous (Rab38 cht/ +) and wild-type mice were examined clinically, histologically, ultrastructurally, and electrophysiologically. Mice homozygous for both the Rab38 cht and the Tyrp1 b alleles were similarly examined.
results. Rab38 cht/cht mice showed variable peripheral iris transillumination defects at 2 months of age. Patches of RPE hypopigmentation were noted clinically in 57% of Rab38 cht/cht eyes and 6% of Rab38 cht/ + eyes. Rab38 cht/cht mice exhibited thinning of the iris and RPE and larger b-wave amplitudes in the scotopic range when compared with the control animals. Compared with wild-type mice, Rab38 cht/cht melanosomes were smaller and there were fewer in neuroectodermally derived retinal pigment epithelium; in neural crest-derived choroid melanocytes, they were smaller in size only. Mutation of both Rab38 and Tyrp1 produced mice with ocular and coat color pigment dilution greater than that seen with either mutation alone. Comprehensive clinical and pathologic analyses showed no other organ system or blood defects in Rab38 cht/cht mice.
conclusions. Rab38 cht/cht mice show ocular characteristics reminiscent of human oculocutaneous albinism, as well as iris and RPE thinning. The synergistic effects of the Rab38 cht and Tyrp1 b alleles suggest that TYRP1 is not the only target of RAB38 trafficking. This mouse line provides a useful model for studying melanosome biology and its role in human ocular diseases.
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