| First Author | Odgren PR | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 4 | Pages | e9959 |
| PubMed ID | 20376364 | Mgi Jnum | J:160175 |
| Mgi Id | MGI:4453533 | Doi | 10.1371/journal.pone.0009959 |
| Citation | Odgren PR, et al. (2010) Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies. PLoS One 5(4):e9959 |
| abstractText | 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. |
