Abstract
BackgroundMutations 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.Methodology/Principal FindingsWe 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 AtrxCol2cre 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/SignificanceThese 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.
Highlights
ATR-X syndrome (Alpha-Thalassemia/Mental Retardation, X-linked) is a human disorder caused by mutations in the ATRX gene[1,2]
Primary chondrocytes in monolayer culture were stained for ATRX by immunofluorescence
Western blots of primary cultured chondrocytes showed that full-length ATRX was expressed in cartilage (Figure 2B)
Summary
ATR-X syndrome (Alpha-Thalassemia/Mental Retardation, X-linked) is a human disorder caused by mutations in the ATRX gene[1,2]. Clinical manifestations include severe psychomotor and mental retardation, characteristic facial features, urogenital abnormalities, skeletal deformities and a-thalassemia [2]. ATR-X syndrome patients display a wide range of skeletal abnormalities, and 66% of patients show dwarfism [4]. Delayed bone age is characteristic of most cases studied by thorough radiological investigation [2]. For some patients, these skeletal abnormalities are apparent at birth, for others they manifest later in life, during the pubertal growth spurt [4]. Mutations in the human ATRX gene cause developmental defects, including skeletal deformities and dwarfism. ATRX encodes a chromatin remodeling protein, the role of ATRX in skeletal development is currently unknown
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