Ochratoxin A induces craniofacial malformation in mice acting on Dlx5 gene expression

Front Biosci (Elite Ed). 2010 Jan 1;2:133-42. doi: 10.2741/e75.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Craniofacial Abnormalities / chemically induced*
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / pathology
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Homeodomain Proteins / metabolism*
  • In Situ Hybridization
  • MSX1 Transcription Factor / metabolism
  • Maternal Exposure*
  • Mice
  • Mice, Inbred C57BL
  • Ochratoxins / toxicity*
  • Pregnancy

Substances

  • Dlx5 protein, mouse
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • Msx1 protein, mouse
  • Ochratoxins
  • ochratoxin A