eScholarship@UMMS

Title

Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies

Authors

Paul R. Odgren, University of Massachusetts Medical SchoolFollow
Craig H. Pratt, Institute for Molecular Biophysics
Carole A. MacKay, University of Massachusetts Medical School
April Mason-Savas, University of Massachusetts Medical SchoolFollow
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

Publication Date

4-1-2010

Document Type

Article

Subjects

Lamins; Mutation

Disciplines

Cell Biology

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.

DOI of Published Version

10.1371/journal.pone.0009959

Source

PLoS One. 2010 Apr 1;5(4):e9959. Link to article on publisher's site

Journal/Book/Conference Title

PloS one

Related Resources

Link to Article in PubMed

PubMed ID

20376364

Repository Citation

Odgren, Paul R.; Pratt, Craig H.; MacKay, Carole A.; Mason-Savas, April; Curtain, Michelle; Shopland, Lindsay S.; Ichicki, Tsutomu; Sundberg, John P.; and Donahue, Leah Rae, "Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies" (2010). Odgren Lab Publications. 2.
https://escholarship.umassmed.edu/odgren/2