Disheveled Hair and Ear (Dhe), a Spontaneous Mouse Lmna Mutation Modeling Human Laminopathies

作者：Odgren Paul R^*; Pratt Craig H; MacKay Carole A; Mason Savas April; Curtain Michelle; Shopland Lindsay; Ichicki Tsutomu; Sundberg John P; Donahue Leah Rae

来源：PLos One, 2010, 5(3): e9959.

DOI：10.1371/journal.pone.0009959

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.

• 出版日期2010-4-1