Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies.
PLoS One 2010; 5(4):e9959.
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.
Odgren, P R.; Pratt, C H.; Mackay, C A.; Mason, Savas A.; Curtain, M; Shopland, L; Ichicki, T; Sundberg, J P.; and Donahue, L R., "Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies." (2010). Faculty Research 2010. 158.