A Dominant-Negative Mutation of Mouse Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation

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Nail-patella syndrome is a human genetic disease caused by an inactivating mutation in one copy of a gene called LMX1B, with the amount of protein produced from the remaining copy of the gene not being enough for normal function. Patients with this disease have malformations of their nails, elbows and kneecaps. Some patients also develop kidney disease and glaucoma. LMX1B controls where and when other genes are expressed and it is important during development. Studies in mice have shown that complete absence of Lmx1b is lethal at birth. In contrast to humans, mice with only one copy of the gene are normal. Here we describe a new mutant mouse, Icst, which has a mutation in Lmx1b that abolishes the ability of the protein to bind near genes that it controls. Mice with one normal and one copy of Lmx1b with the Icst mutation have eye defects and some die shortly after birth probably due to kidney failure. Therefore having one functional and one mutant copy of Lmx1b is more detrimental than having a half dose of functional protein. The Icst mouse is a model of human glaucoma where mutation of the same gene causes glaucoma in humans and mice.

Vyšlo v časopise: A Dominant-Negative Mutation of Mouse Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004359
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004359

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