TY - JOUR
T1 - Foxn3 is essential for craniofacial development in mice and a putative candidate involved in human congenital craniofacial defects
AU - Samaan, George
AU - Yugo, Danielle
AU - Rajagopalan, Sangeetha
AU - Wall, Jonathan
AU - Donnell, Robert
AU - Goldowitz, Dan
AU - Gopalakrishnan, Rajaram
AU - Venkatachalam, Sundaresan
N1 - Funding Information:
This work was supported by the Physicians Medical Education and Research Foundation and start-up funds from the UTK BCMB department.
PY - 2010/9
Y1 - 2010/9
N2 - The fork-head transcription factors are involved in a variety of physiological processes including development, aging, obesity, and cancer. The fork-head transcription factor FOXN3 has been implicated in cell cycle and transcription regulation at the cellular level. However, the physiological functions of FOXN3 in mammals are not known. To understand the role of the fork-head transcription factor FOXN3 in mammalian development, we have generated a mutant mouse model for the Foxn3 gene. Our analysis shows that the Foxn3 mutation leads to partial embryonic and postnatal lethality, growth retardation, eye formation defects, dental anomalies and craniofacial defects. Foxn3 mutant tissues and cells are also defective in the expression of distinct osteogenic genes. Interestingly, the phenotypes of Foxn3 mutant mice show a striking overlap with the clinical features of human patients with congenital defects and chromosomal aberrations involving the human FOXN3 locus. More than three fourths of human congenital disorders involve craniofacial malformations and a majority of the perturbed genetic components that lead to such disorders are yet to be identified. Our results implicate a role for the FOXN3 gene in the etiology of craniofacial defects in humans.
AB - The fork-head transcription factors are involved in a variety of physiological processes including development, aging, obesity, and cancer. The fork-head transcription factor FOXN3 has been implicated in cell cycle and transcription regulation at the cellular level. However, the physiological functions of FOXN3 in mammals are not known. To understand the role of the fork-head transcription factor FOXN3 in mammalian development, we have generated a mutant mouse model for the Foxn3 gene. Our analysis shows that the Foxn3 mutation leads to partial embryonic and postnatal lethality, growth retardation, eye formation defects, dental anomalies and craniofacial defects. Foxn3 mutant tissues and cells are also defective in the expression of distinct osteogenic genes. Interestingly, the phenotypes of Foxn3 mutant mice show a striking overlap with the clinical features of human patients with congenital defects and chromosomal aberrations involving the human FOXN3 locus. More than three fourths of human congenital disorders involve craniofacial malformations and a majority of the perturbed genetic components that lead to such disorders are yet to be identified. Our results implicate a role for the FOXN3 gene in the etiology of craniofacial defects in humans.
KW - Craniofacial
KW - Fork-head
KW - Foxn3
KW - Mammalian development
KW - Mouse model
KW - Transcription factor
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U2 - 10.1016/j.bbrc.2010.07.142
DO - 10.1016/j.bbrc.2010.07.142
M3 - Article
C2 - 20691664
AN - SCOPUS:78650852967
SN - 0006-291X
VL - 400
SP - 60
EP - 65
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -