title: Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2.
abstract: The nfkb1 and nfkb2 genes encode closely related products regulating immune and inflammatory responses. Their role during development and differentiation remains unclear. The generation of nfkb1 null mice (p50-/-) resulted in altered immune responses, but had no effect on development. Similarly, nfkb2 knockout mice (p52-/-) did not show developmental defects (J.C. et al., manuscript submitted). We have investigated the potential for in vivo compensatory functions of these genes by generating double-knockout mice. The surprising result was that the animals developed osteopetrosis because of a defect in osteoclast differentiation, suggesting redundant functions of NF-kappaB1 and NF-kappaB2 proteins in the development of this cell lineage. The osteopetrotic phenotype was rescued by bone marrow transplantation, indicating that the hematopoietic component was impaired. These results define a new mouse osteopetrotic mutant and implicate NF-kappaB proteins in bone development, raising new directions in the treatment of bone disorders.
authors.affiliation: Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
authors.forename: V
authors.initials: V
authors.lastname: Iotsova
authors.forename: J
authors.initials: J
authors.lastname: Caamaño
authors.forename: J
authors.initials: J
authors.lastname: Loy
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Lewin
authors.forename: R
authors.initials: R
authors.lastname: Bravo
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000235:genetics; D002454:Cell Differentiation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016328:NF-kappa B / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D010010:Osteoclasts / Q000166:cytology; D010022:Osteopetrosis / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit