title: Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Dhe mice should provide a useful new model for investigations of the pathogenesis of laminopathies.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Odgren
authors.forename: Craig H
authors.initials: CH
authors.lastname: Pratt
authors.forename: Carole A
authors.initials: CA
authors.lastname: Mackay
authors.forename: April
authors.initials: A
authors.lastname: Mason-Savas
authors.forename: Michelle
authors.initials: M
authors.lastname: Curtain
authors.forename: Lindsay
authors.initials: L
authors.lastname: Shopland
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ichicki
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.forename: Leah Rae
authors.initials: LR
authors.lastname: Donahue
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D000072261:Dishevelled Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D017354:Point Mutation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D034904:Lamin Type A; D010750:Phosphoproteins