Ochratoxin A induces craniofacial malformation in mice acting on Dlx5 gene expression.
Ochratoxin A (OTA) is a mycotoxin produced by fungal of Aspergillus species absorbed in human through contaminate food in gastrointestinal tract. OTA has been demonstrated to be teratogenic in a number of species including mice and potentially human. Mice exposed in uterus to OTA develop craniofacial abnormalities such as exencephaly, microencephaly, microphthalmia and facial clefts. An important role in differentiation of maxillofacial are exerted by the Hox related genes Dlx and Msx. In the present investigation we have confirmed that 2.75 mg/kg body weight OTA, given at gestational day 7.5, induces significant developmental craniofacial anomalies in mice and we have demonstrated the down expression of Dlx5, a member of Dlx gene family, that seems to be responsible of the observed deformities. These results support the hypothesis that Dlx5 is a target for ochratoxin and the inhibition of its function, directly or indirectly, could be at origin of the observed differentiation defects.
Napoletano
Margherita
M
Institute of Genetics and Biophysics A Buzzati Traverso CNR, Naples, Italy.
Pennino
Davide
D
Izzo
Gaia
G
de Maria
Salvatore
S
Ottaviano
Raffaele
R
Ricciardi
Maddalena
M
Mancini
Roberto
R
Schiattarella
Antonella
A
Farina
Ernesto
E
Metafora
Salvatore
S
Cartenì
Maria
M
Ritieni
Alberto
A
Minucci
Sergio
S
Morelli
Franco
F
D000818:Animals; D019465:Craniofacial Abnormalities / Q000139:chemically induced*; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D051957:MSX1 Transcription Factor / Q000378:metabolism; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D009793:Ochratoxins / Q000633:toxicity*; D011247:Pregnancy
C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D009793:Ochratoxins; C025589:ochratoxin A