Loss of ATRX in chondrocytes has minimal effects on skeletal development.
BACKGROUND
Mutations in the human ATRX gene cause developmental defects, including skeletal deformities and dwarfism. ATRX encodes a chromatin remodeling protein, however the role of ATRX in skeletal development is currently unknown.


RESULTS
We induced Atrx deletion in mouse cartilage using the Cre-loxP system, with Cre expression driven by the collagen II (Col2a1) promoter. Growth rate, body size and weight, and long bone length did not differ in Atrx(Col2cre) mice compared to control littermates. Histological analyses of the growth plate did not reveal any differences between control and mutant mice. Expression patterns of Sox9, a transcription factor required for cartilage morphogenesis, and p57, a marker of cell cycle arrest and hypertrophic chondrocyte differentiation, was unaffected. However, loss of ATRX in cartilage led to a delay in the ossification of the hips in some mice. We also observed hindlimb polydactily in one out of 61 mutants.


CONCLUSIONS
These findings indicate that ATRX is not directly required for development or growth of cartilage in the mouse, suggesting that the short stature in ATR-X patients is caused by defects in cartilage-extrinsic mechanisms.
Department of Biochemistry, University of Western Ontario, London, Ontario, Canada.
Lauren A
LA
Solomon
Jennifer R
JR
Li
Nathalie G
NG
Bérubé
Frank
F
Beier
D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000075924:X-linked Nuclear Protein
C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D004265:DNA Helicases; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein