title: Pulmonary pathologies in pallid mice result from nonhematopoietic defects.
abstract: Several single gene pigment mutants of inbred C57BL/6J mice display a triad of subcellular granule-associated defects: oculocutaneous pigment dilution, prolonged bleeding due to defects in platelet dense granules, and abnormal lysosomes. These features also characterize Hermansky-Pudlak Syndrome (HPS), making these mice relevant animal models for HPS. Mice of one mutant strain, pallid, in addition to the hallmark triad of signs, also exhibit age-dependent lung pathology. Respiratory system mechanics showed that the age-dependent histopathology of pallid mice was accompanied by a decrease in lung reactance. Furthermore, the possibility that pallid pulmonary pathology may result from persistent inflammation due to microhemorrhage owing to the platelet defect was examined. Hematopoietic reconstitution of pallid mice with marrow from normal C57BL/6J donors did not prevent the development of the pulmonary histopathology or respiratory system mechanics characteristic of the pallid genotype. Similarly, wild-type mice 12 months after engraftment with pallid marrow did not develop pallid-like pulmonary histopathology or respiratory system mechanics. Thus, pallid-associated pulmonary functional and structural pathologies are not linked to the marrow (bleeding) genotype, but instead are the result of an age-dependent process resulting from a defect(s) in one or more nonhematopoietic cell types.
authors: Department of Biochemistry and Molecular Biology, S. C. Johnson Research Building, Scottsdale, Arizona 85259, USA.
authors: Michael P
authors: MP
authors: McGarry
authors: Michael
authors: M
authors: Borchers
authors: Edward K
authors: EK
authors: Novak
authors: Nancy A
authors: NA
authors: Lee
authors: Patricia J
authors: PJ
authors: Ohtake
authors: James J
authors: JJ
authors: Lee
authors: Richard T
authors: RT
authors: Swank
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010859:Pigmentation Disorders / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D015656:Respiratory Mechanics