title: Analysis of ocular hypopigmentation in Rab38cht/cht mice.
abstract: OBJECTIVE
  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.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. brooksb@mail.nih.gov
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: Denise M
authors.initials: DM
authors.lastname: Larson
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Sten
authors.initials: S
authors.lastname: Kjellstrom
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Mary A
authors.initials: MA
authors.lastname: Crawford
authors.forename: Lynn
authors.initials: L
authors.lastname: Lamoreux
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: Richard
authors.initials: R
authors.lastname: Hess
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiao
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Arvydas
authors.initials: A
authors.lastname: Maminishkis
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
authors.forename: Ronald
authors.initials: R
authors.lastname: Bush
authors.forename: William J
authors.initials: WJ
authors.lastname: Pavan
mesh_terms: D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D015862:Choroid Diseases / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006200:Hair Color; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D007499:Iris Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D020460:Melanosomes / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010088:Oxidoreductases / Q000235:genetics; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000648:ultrastructure; D020641:Polymorphism, Single Nucleotide; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C412058:RAB38 protein, human; C498786:Rab38 protein, mouse; D020691:rab GTP-Binding Proteins