title: Postnatal growth defect in mice upon persistent Hoxa2 expression in the chondrogenic cell lineage.
abstract: Hoxa2 is a homeotic transcription factor, which is downregulated once chondrogenic differentiation is initiated. We previously generated a transgenic mouse model, which turns Hoxa2 on in cells expressing Collagen II A1, i.e. in cells entering chondrogenesis. As a consequence, mice display a general embryonic delay of ossification and then a postnatal growth defect. Col2a1-Cre mice were crossed with an inducible β-actin driven Hoxa2 transgene. Spines, vertebrae and limbs were measured and skeletal elements were studied by X-ray, microCT, pQCT, TEM, western-blotting, histomorphometry and immunohistochemistry. Mice expressing Hoxa2 in chondrogenic cells feature a proportionate short stature phenotype with a severe lordosis, which appeared significant from postnatal day 4. Analysis of both cartilage and bone development in affected embryos and mice from birth till P35 did not reveal any major defect in histogenesis, except a reduced number of chondrocytes in the vertebral anlage at E13.5. In conclusion, the sustained expression of Hoxa2 in the chondrocyte lineage is characterized by a proportionate short stature resulting from skeletal growth defect. The indepth analysis of cartilage and bone histogenesis points towards an initial deficit in cell mobilization to enter chondrogenesis.
authors.affiliation: Pôle de Morphologie, Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium. deprez.pierre@uclouvain.be
authors.forename: Pierre Marcel Louis
authors.initials: PM
authors.lastname: Deprez
authors.forename: Miloud Georges
authors.initials: MG
authors.lastname: Nichane
authors.forename: Pierre
authors.initials: P
authors.lastname: Rousseaux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Devogelaer
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappard
authors.forename: Benoît Georges
authors.initials: BG
authors.lastname: Lengelé
authors.forename: René
authors.initials: R
authors.lastname: Rezsöhazy
authors.forename: Catherine
authors.initials: C
authors.lastname: Nyssen-Behets
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis / Q000235:genetics*; D024043:Collagen Type II / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D008141:Lordosis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009139:Musculoskeletal Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics; D011859:Radiography
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse