Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia.

[22q11.2 deletion syndrome]

T -box transcription factor , TBX 1 , is the major candidate gene for 22 q 11 .2 deletion syndrome (DiGeorge / Velo-cardio-facial syndrome ) characterized by facial defects , thymus hypoplasia , cardiovascular anomalies and cleft palates . Here , we report that the loss of Tbx 1 in mouse (Tbx 1 (-/-)) results in skeletal abnormalities similar to those of cleidocranial dysplasia (CCD ) in humans , which is an autosomal-dominant skeletal disease caused by mutations in RUNX 2 . Tbx 1 (-/-) mice display short stature , absence of hyoid bone , failed closure of fontanelle , bifid xiphoid process and hypoplasia of clavicle and zygomatic arch . A cell-type -specific deletion of Tbx 1 in osteochondro-progenitor (Tbx 1 (OPKO )) or mesodermal (Tbx 1 (MKO )) lineage partially recapitulates the Tbx 1 (-/-) bone phenotypes . Although Tbx 1 expression has not been previously reported in neural crest , inactivation of Tbx 1 in the neural crest lineage (Tbx 1 (NCKO )) leads to an absence of the body of hyoid bone and postnatal lethality , indicating an unanticipated role of Tbx 1 in neural crest development . Indeed , Tbx 1 is expressed in the neural crest-derived hyoid bone primordium , in addition to mesoderm-derived osteochondral progenitors . Ablation of Tbx 1 affected Runx 2 expression in calvarial bones and overexpression of Tbx 1 induced Runx 2 expression in vitro . Taken together , our current studies reveal that Tbx 1 is required for mesoderm- and neural crest-derived osteoblast differentiation and normal skeletal development . TBX 1 mutation could lead to CCD-like bone phenotypes in human .

Diseases
Validation

Diseases presenting "facial defects" symptom

22q11.2 deletion syndrome

dentinogenesis imperfecta

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