Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies.
Document Type
Article
Publication Date
2010
JAX Source
PLoS One 2010; 5(4):e9959.
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.
Recommended Citation
Odgren PR,
Pratt CH,
Mackay CA,
Mason SA,
Curtain M,
Shopland L,
Ichicki T,
Sundberg JP,
Donahue LR.
Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies. PLoS One 2010; 5(4):e9959.