disheveled hair and ear (dhe), a spontaneous mouse lmna mutation modeling human laminopathies凌乱的头发和耳朵(她),鼠标lmna自发突变人类laminopathies建模.pdfVIP

Disheveled Hair and Ear (Dhe), a Spontaneous Mouse Lmna Mutation Modeling Human Laminopathies 1 2,4 1¤a 1 3,4 Paul R. Odgren , Craig H. Pratt , Carole A. MacKay , April Mason-Savas , Michelle Curtain , Lindsay 2,4 4¤b 4 3,4 Shopland , Tsutomu Ichicki , John P. Sundberg , Leah Rae Donahue * 1 Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2 Institute for Molecular Biophysics, Bar Harbor, Maine, United States of America, 3 Genetic Resource Science, Bar Harbor, Maine, United States of America, 4 The Jackson Laboratory, Bar Harbor, Maine, United States of America 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