Details

Autor(en) / Beteiligte

• Vacher, Jean
• Chalhoub, Nader
• Benachenhou, Nadia
• Rajapurohitam, Venkatesh
• Pata, Monica
• Ferron, Mathieu
• Frattini, Annalisa
• Villa, Anna

Titel

Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human

Ist Teil von

• Nature medicine, 2003-04, Vol.9 (4), p.399-406

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• The spontaneous mouse grey-lethal (gl) mutation is responsible for a coat color defect and for the development of the most severe autosomal recessive form of osteopetrosis. Using a positional cloning approach, we have mapped and isolated the gl locus from a approximately 1.5 cM genetic interval. The gl locus was identified in a bacterial artificial chromosome (BAC) contig by functional genetic complementation in transgenic mice. Genomic sequence analysis revealed that the gl mutation is a deletion resulting in complete loss of function. The unique approximately 3 kb wild-type transcript is expressed primarily in osteoclasts and melanocytes as well as in brain, kidney, thymus and spleen. The gl gene is predicted to encode a 338-amino acid type I transmembrane protein that localizes to the intracellular compartment. Mutation in the human GL gene leads to severe recessive osteopetrosis. Our studies show that mouse Gl protein function is absolutely required for osteoclast and melanocyte maturation and function.