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

Baojie Li, Sharon Boast, Kenia De Los Santos, Ira Schieren, Marisol Quiroz, Steven L. Teitelbaum, M. Mehrdad Tondravi, Stephen P. Goff

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

The c-Abl protein is a non-receptor tyrosine kinase involved in many aspects of mammalian development, c-Abl kinase is widely expressed, but high levels are found in hyaline cartilage in the adult, bone tissue in newborn mice, and osteoblasts and associated neovasculature at sites of endochondrial ossification in the fetus. Mice homozygous for mutations in the gene encoding c-Abl (Abl) display increased perinatal mortality, reduced fertility, foreshortened crania and defects in the maturation of B cells in bone marrow. Here we demonstrate that Abl(-/-) mice are also osteoporotic. The long bones of mutant mice contain thinner cortical bone and reduced trabecular 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. Osteoblasts from both stromal and calvarial explants showed delayed maturation in vitro as measured by expression of alkaline phosphatase (ALP), induction of mRNA encoding osteocalcin and mineral deposition.

Original languageEnglish
Pages (from-to)304-308
Number of pages5
JournalNature Genetics
Volume24
Issue number3
DOIs
StatePublished - Mar 2000

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