Pulmonary pathologies in pallid mice result from nonhematopoietic defects

Michael P. McGarry, Michael Borchers, Edward K. Novak, Nancy A. Lee, Patricia J. Ohtake, James J. Lee, Richard T. Swank

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalExperimental and Molecular Pathology
Volume72
Issue number3
DOIs
StatePublished - Jan 1 2002

Keywords

  • Bone marrow transplant
  • Hermansky-Pudlak Syndrome
  • Lung
  • Pallid mouse
  • Phenotype
  • Pigment mutant
  • Pulmonary pathology
  • Reactance
  • Respiratory mechanics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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