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Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies
Odgren Lab
  • Paul R. Odgren, University of Massachusetts Medical School
  • Craig H. Pratt, Institute for Molecular Biophysics
  • Carole A. MacKay, University of Massachusetts Medical School
  • April Mason-Savas, University of Massachusetts Medical School
  • Michelle Curtain, Genetic Resource Science
  • Lindsay S. Shopland, University of Massachusetts Medical School
  • Tsutomu Ichicki, The Jackson Laboratory
  • John P. Sundberg, The Jackson Laboratory
  • Leah Rae Donahue, Genetic Resource Science
UMMS Affiliation
Department of Cell Biology
Date
4-1-2010
Document Type
Article
Medical Subject Headings
Lamins; Mutation
Disciplines
Abstract
BACKGROUND: Investigations of naturally-occurring mutations in animal models provide important insights and valuable disease models. Lamins A and C, along with lamin B, are type V intermediate filament proteins which constitute the proteinaceous boundary of the nucleus. LMNA mutations in humans cause a wide range of phenotypes, collectively termed laminopathies. To identify the mutation and investigate the phenotype of a spontaneous, semi-dominant mutation that we have named Disheveled hair and ear (Dhe), which causes a sparse coat and small external ears in heterozygotes and lethality in homozygotes by postnatal day 10. FINDINGS: Genetic mapping identified a point mutation in the Lmna gene, causing a single amino acid change, L52R, in the coiled coil rod domain of lamin A and C proteins. Cranial sutures in Dhe/+ mice failed to close. Gene expression for collagen types I and III in sutures was deficient. Skulls were small and disproportionate. Skeletons of Dhe/+ mice were hypomineralized and total body fat was deficient in males. In homozygotes, skin and oral mucosae were dysplastic and ulcerated. Nuclear morphometry of cultured cells revealed gene dose-dependent blebbing and wrinkling. CONCLUSION: Dhe mice should provide a useful new model for investigations of the pathogenesis of laminopathies.
Rights and Permissions
Citation: PLoS One. 2010 Apr 1;5(4):e9959. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
20376364
Citation Information
Paul R. Odgren, Craig H. Pratt, Carole A. MacKay, April Mason-Savas, et al.. "Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies" Vol. 5 Iss. 4 (2010) ISSN: 1932-6203 (Linking)
Available at: http://works.bepress.com/paul_odgren/12/