Open AccessIdentification of 14-3-3σ mutation causing cutaneous abnormality in repeated-epilation mutant mouse
Author(s) -
Qiutang Li,
Qin Lu,
Gabriela Estepa,
Inder M. Verma
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0508310102
Subject(s) - mutant , biology , microbiology and biotechnology , mutation , phenotype , gene , genetics , ectopic expression
Repeated-epilation (Er ) mutation in the mouse is inherited as an autosomal and semidominant mutation. Major defects in heterozygous adults and homozygous fetuses were associated with skin and were caused by abnormal ectodermal differentiation. Heterozygous mice are characterized by repeated hair loss and regrowth, and homozygous fetuses die at birth with severe abnormality in skin, limb, tail, and face. To identify the gene causingEr mutation, we have performed gene-expression profiles of skins and mouse embryonic fibroblasts from WT and mutantEr mice by using Affymetrix (Santa Clara, CA) chip analysis. By analyzing the candidate genes generated from gene-expression profiling, we identified aSfn mutation inEr mice. A single nucleotide insertion in theSfn (Stratifin, also called 14-3-3σ) coding region results in a truncated protein lacking 40 amino acid residues at the C terminus. The mutation is linked with phenotypes ofEr -heterozygous and -homozygous mice. Ectopic overexpression of WT 14-3-3σ inEr/Er keratinocytes rescues defects in keratinocyte differentiation. Our study demonstrates that 14-3-3σ is a crucial regulator for skin proliferation and differentiation.