title: Dsp rul: a spontaneous mouse mutation in desmoplakin as a model of Carvajal-Huerta syndrome.
abstract: Studies of spontaneous mutations in mice have provided valuable disease models and important insights into the mechanisms of human disease. Ruffled (rul) is a new autosomal recessive mutation causing abnormal hair coat in mice. The rul allele arose spontaneously in the RB156Bnr/EiJ inbred mouse strain. In addition to an abnormal coat texture, we found diffuse epidermal blistering, abnormal electrocardiograms (ECGs), and ventricular fibrosis in mutant animals. Using high-throughput sequencing (HTS) we found a frameshift mutation at 38,288,978bp of chromosome 13 in the desmoplakin gene (Dsp). The predicted mutant protein is truncated at the c-terminus and missing the majority of the plakin repeat domain. The phenotypes found in Dsp(rul) mice closely model a rare human disorder, Carvajal-Huerta syndrome. Carvajal-Huerta syndrome (CHS) is a rare cardiocutaneous disorder that presents in humans with wooly hair, palmoplantar keratoderma and ventricular cardiomyopathy. CHS results from an autosomal recessive mutation on the 3' end of desmoplakin (DSP) truncating the full length protein. The Dsp(rul) mouse provides a new model to investigate the pathogenesis of CHS, as well as the underlying basic biology of the adhesion molecules coded by the desmosomal genes.
authors: The Jackson Laboratory, Bar Harbor, ME, USA. Electronic address: herbert.pratt@jax.org.
authors: C
authors: C
authors: Herbert Pratt
authors: The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
authors: Christopher S
authors: CS
authors: Potter
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Heather
authors: H
authors: Fairfield
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Laura G
authors: LG
authors: Reinholdt
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: David E
authors: DE
authors: Bergstrom
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Belinda S
authors: BS
authors: Harris
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Ian
authors: I
authors: Greenstein
authors: Dept. of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Soheil S
authors: SS
authors: Dadras
authors: Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, CT, USA.
authors: Bruce T
authors: BT
authors: Liang
authors: Dept. of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK.
authors: Paul N
authors: PN
authors: Schofield
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: John P
authors: JP
authors: Sundberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D009202:Cardiomyopathies / Q000235:genetics*; D002311:Cardiomyopathy, Dilated; D051180:Desmoplakins / Q000235:genetics*; D016368:Frameshift Mutation; D008040:Genetic Linkage / Q000235:genetics; D006197:Hair / Q000473:pathology*; D006201:Hair Diseases / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
chemical_list: D051180:Desmoplakins; C495295:Dsp protein, mouse
keywords: Carvajal-Huerta syndrome; Dsp; Gene networks; Hair shaft; Mouse model