Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation

The c-Abl protein is a non-receptor tyrosine kinase involved in many aspect s of mammalian development. c-Abl kinase is widely expressed, but high leve ls are found in hyaline cartilage in the adult, bone tissue in newborn mice , and osteoblasts and associated neovasculature at sites of endochondrial o ssification in the fetus(1,2). Mice homozygous for mutations in the gene en coding c-Abl (Abl) display increased perinatal mortality, reduced fertility , foreshortened crania and defects in the maturation of B cells in bone mar row(3,4). Here we demonstrate that Abl(-/-) mice are also osteoporotic. The long bones of mutant mice contain thinner cortical bone and reduced trabec ular bone volume. The osteoporotic phenotype is not due to accelerated bone turnover-both the number and activity of osteoclasts are similar to those of control littermates-but rather to dysfunctional osteoblasts. In addition , the rate of mineral apposition in the mutant animals is reduced. Osteobla sts from both stromal and calvarial explants showed delayed maturation in v itro as measured by expression of alkaline phosphatase (ALP), induction of mRNA encoding osteocalcin and mineral deposition.