title: The Noggin null mouse phenotype is strain dependent and haploinsufficiency leads to skeletal defects.
abstract: Noggin is a secreted peptide that binds and inactivates Bone Morphogenetic Proteins, members of the transforming growth factor beta superfamily of secreted signaling molecules. In vertebrate limbs, Noggin is expressed in condensing cartilage and immature chondrocytes. Inactivation of the Noggin gene has been reported in an inbred 129X1/SvJ mouse genetic background. The null allele was lethal at 18.5 dpc and resulted in severe hyperplasia of the cartilage together with multiple joint fusions. In order to investigate the effect of the genetic background on the phenotypic manifestation of Noggin inactivation, we crossed the Noggin null allele into the outbred CD1 and inbred DBA1 and C57BL/6 mouse strains. We describe here skeletal phenotypes of Noggin null mice, such as accelerated or delayed mineralization of different bones suggestive of a complex tissue response to the perturbations in BMP balances. Additionally, we found that in the absence of Noggin, early specification of myogenic differentiation was unaffected, whereas terminal stages of myogenesis were delayed. Furthermore, we have discovered Noggin haploinsufficiency leading to carpal and tarsal fusions reminiscent of some phenotypes reported for NOGGIN haploinsufficiency in humans.
authors.affiliation: University of Leuven, Leuven, Belgium.
authors.forename: Przemko
authors.initials: P
authors.lastname: Tylzanowski
authors.forename: Liese
authors.initials: L
authors.lastname: Mebis
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology*; D002352:Carrier Proteins / Q000235:genetics*; D005121:Extremities / Q000196:embryology; D017880:Limb Deformities, Congenital / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000002:abnormalities / Q000196:embryology; D012867:Skin / Q000196:embryology; D012868:Skin Abnormalities / Q000235:genetics; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D000099176:Noggin Protein