Sunday, October 17, 2010

Hoxa2

Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature.

"In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature.  This overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. The persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9{up} and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively."



"Sox9 induction relies on Pax1{up} and Pax9 through Bapx1 stimulation"

"Bmp7 null animals present a severe postnatal size reduction"

"Pax9 and Sox6 deficient mice did not feature length reduction, despite the presence of an
impressive phenotype when associated with a loss-of-function of their usual partners Pax1"

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