Overexpression of mouse TTF-2 gene causes cleft palate.
In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF-2 null mice (TTF-2(-/-) ) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3-TTF-2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF-2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF-2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF-2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF-2 transgenic mice. These observations suggest that overexpression of TTF-2 during palatogenesis may contribute to formation of cleft palate.
State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
Tian
T
Meng
Jia-Yu
JY
Shi
Min
M
Wu
Yan
Y
Wang
Ling
L
Li
Yan
Y
Liu
Qian
Q
Zheng
Lei
L
Huang
Bing
B
Shi
D000818:Animals; D002972:Cleft Palate / Q000235:genetics*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010159:Palate / Q000196:embryology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated
D051858:Forkhead Transcription Factors; C472789:Foxe1 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D012333:RNA, Messenger; D022661:RNA, Untranslated