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

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.

Characterization and expression analyses of the mouse Wiskott-Aldrich syndrome protein (WASP) family member Wave1/Scar.

Characterization of multiprotein complexes involved in actin remodeling and cytoskeleton reorganization is essential to understand the basic mechanisms of cell motility and migration. To identify proteins implicated in these processes, we have isolated the mouse Wave1/Scar gene, a member of the Wiskott-Aldrich syndrome protein (WASP) family. The mouse Wave1 gene was physically localized on chromosome 10 and spans over 12 Kb comprising eight exons and seven introns.

Physical and transcriptional map of the mouse Chromosome 10 proximal region syntenic to human 6q16-q21.

Toward the isolation of the grey-lethal (gl) gene, we have genetically localized this locus on mouse Chromosome (Chr) 10 between the Fyn gene and the D10Mit148 microsatellite marker. Here, we have screened five yeast artificial chromosome (YAC) libraries and isolated more than 100 YAC clones mapping to this region. Forty-two clones were characterized and assembled in an approximately 8.

The mouse osteopetrotic grey-lethal mutation induces a defect in osteoclast maturation/function.

The osteopetrotic grey-lethal (gl) mouse mutant displays many similarities to the human malignant autosomal-recessive form of osteopetrosis. In this study, we show that the gl osteopetrotic bone phenotype is characterized by the presence of numerous differentiated multinucleated osteoclasts. A significant increase in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was detected in vivo, suggesting induction of differentiation in the osteoclast lineage as a compensatory mechanism.

Frequent loss of heterozygosity at the DNA mismatch-repair loci hMLH1 and hMSH3 in sporadic breast cancer.

To study the involvement of DNA mismatch-repair genes in sporadic breast cancer, matched normal and tumoral DNA samples of 22 patients were analysed for genetic instability and loss of heterozygosity (LOH) with 42 microsatellites at or linked to hMLH1 (3p21), hMSH2 (2p16), hMSH3 (5q11-q13), hMSH6 (2p16), hPMS1 (2q32) and hPMS2 (7p22) loci. Chromosomal regions 3p21 and 5q11-q13 were found hemizygously deleted in 46% and 23% of patients respectively. Half of the patients deleted at hMLH1 were also deleted at hMSH3.