Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination.

Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and immunoglobulin class switching in activated B cells. Because AID has no known target-site specificity, there have been efforts to identify non-immunoglobulin AID targets. We show here that AID acts promiscuously, generating widespread DNA double-strand breaks (DSBs), genomic instability and cytotoxicity in B cells with less homologous recombination ability.

Sex-specific regulation of body size and bone slenderness by the acid labile subunit.

Insulin-like growth factor 1 (IGF-1) is a crucial mediator of body size and bone mass during growth and development. In serum, IGF-1 is stabilized by several IGF-1-binding proteins (IGFBPs) and the acid labile subunit (ALS). Previous research using ALS knockout (ALSKO) mice indicated a growth retardation phenotype, and clinical reports of humans have indicated short stature and low bone mineral density (BMD) in patients with ALS deficiency.

A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis.

A spontaneous mouse mutant, designated 'small' (sml), was recognized by reduced body size suggesting a defect in the IGF1/GH axis. The mutation was mapped to the chromosome 1 region containing Irs1, a viable candidate gene whose sequence revealed a single nucleotide deletion resulting in a premature stop codon. Despite normal mRNA levels in mutant and control littermate livers, western blot analysis revealed no detectable protein in mutant liver lysates.