| First Author | Moran JL | Year | 2007 |
| Journal | J Invest Dermatol | Volume | 127 |
| Issue | 8 | Pages | 1893-7 |
| PubMed ID | 17429434 | Mgi Jnum | J:119554 |
| Mgi Id | MGI:3702758 | Doi | 10.1038/sj.jid.5700825 |
| Citation | Moran JL, et al. (2007) A mouse mutation in the 12R-Lipoxygenase, Alox12b, disrupts formation of the epidermal permeability barrier. J Invest Dermatol 127(8):1893-7 |
| abstractText | 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. |
