Retinoic acid deficiency during gastrulation induces craniofacial malformations in mouse resembling fetal alcohol syndrome
Loading...
Date
2017
Authors
Petrelli, Berardino
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Fetal Alcohol Spectrum Disorder is caused by maternal consumption of alcohol during
pregnancy, and the clinical term given to children with birth defects, behavioral difficulties, and cognitive impairments. It can be associated with other co-morbidities which include heart defects, malocclusions, hearing loss, and immune deficiencies. Vitamin A Deficiency (retinoic acid deficiency) is caused by maternal deficiency of Vitamin A (retinol) (and consequently its active metabolite retinoic acid), and is the clinical term given to babies/children who present with (night) blindness, craniofacial malformations, brain aberrations and many of the FASD co-morbidities like heart defects, malocclusions, and immune deficiencies to name a few. The linking of these two streams of research lies in the family of enzymes both pathways share to convert their respective metabolites: ethanol to acetic acid and Vitamin A (retinol) to retinoic acid. The Vitamin A hypothesis suggests that during a binge exposure of alcohol the family of enzymes required to convert retinol to retinoic acid instead converts ethanol to acetic acid, causing the craniofacial malformations, brain aberrations, and co-morbidities present in both
disorders. This paper will present a genetically modified mouse that biochemically mimics
retinoic acid deficiency producing the craniofacial malformations and brain aberrations
comparable to those found in PAE mouse models and clinical FASD outcomes.
Description
Keywords
Retinoic acid, Fetal alcohol spectrum disorder, Craniofacial malformations, FASD, Vitamin A deficiency