title: A mouse mutation in the 12R-lipoxygenase, Alox12b, disrupts formation of the epidermal permeability barrier.
abstract: Nonbullous congenital ichthyosiform erythroderma (NCIE) is a nonsyndromic form of autosomal recessive congenital ichthyosis characterized by hyperkeratosis and a disruption in the epidermal permeability barrier. Identification of mutations in two lipoxygenases (LOXs), ALOX12B (12R-LOX) and ALOXE3 (eLOX3), and further functional studies implicate ALOX12B and ALOXE3 in the etiology of NCIE. Here, we report a mutation in Alox12b in the recessive ethylnitrosurea-induced mouse mutant, mummy (Alox12b(mmy-Bei)). mummy mutants have red, scaly skin and die perinatally. Histologically, mummy mutants display defects in the epidermis. We mapped mummy to a 1.9 Mb interval on Chr. 11 containing Alox12b (12R-LOX), Aloxe3 (eLOX3) and Alox15b (8-LOX). Sequencing of all three genes identified a nonsense mutation in the catalytic domain of Alox12b. We demonstrate that mummy mutants have a disrupted epidermal permeability barrier and that the nonsense mutation in mummy abolishes the enzyme activity of 12R-LOX. The mummy mutant provides a mouse model for LOX-mediated NCIE and is the first described mouse mutant affecting epidermal barrier formation identified by forward genetics.
authors: Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. jmoran@rics.bwh.harvard.edu
authors: Jennifer L
authors: JL
authors: Moran
authors: Haiyan
authors: H
authors: Qiu
authors: Annick
authors: A
authors: Turbe-Doan
authors: Yujuan
authors: Y
authors: Yun
authors: William E
authors: WE
authors: Boeglin
authors: Alan R
authors: AR
authors: Brash
authors: David R
authors: DR
authors: Beier
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000502:physiology*; D018389:Codon, Nonsense; D004817:Epidermis / Q000378:metabolism*; D005838:Genotype; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D051379:Mice; D010539:Permeability
chemical_list: D018389:Codon, Nonsense; D001092:Arachidonate 12-Lipoxygenase