Variations in maternal vitamin A intake modifies phenotypes in a mouse model of 22q11.2 deletion syndrome.

Background: Vitamin A regulates patterning of the pharyngeal arches, cranial nerves, and hindbrain that are essential for feeding and swallowing. In the LgDel mouse model of 22q11.2 deletion syndrome (22q11DS), morphogenesis of multiple structures involved in feeding and swallowing are dysmorphic.

Elevated urine oxalate and renal calculi in a classic galactosemia patient on soy-based formula.

Classic galactosemia results from a deficiency in the galactose-1-phosphate uridylyltransferase (GALT) enzyme, which is essential for galactose metabolism. Treatment focuses on lactose restriction and is achieved with a soy-based diet. Previously, renal calculi have not been documented in galactosemia patients.

High levels of iron supplementation prevents neural tube defects in the Fpn1 mouse model.

Background: Periconception maternal nutrition and folate in particular are important factors influencing the incidence of neural tube defects (NTDs). Many but not all NTDs are prevented by folic acid supplementation and there is a pressing need for additional strategies to prevent these birth defects. Other micronutrients such as iron are potential candidates, yet a clear role for iron deficiency in contributing to NTDs is lacking.

Supt20 is required for development of the axial skeleton.

Somitogenesis and subsequent axial skeletal development is regulated by the interaction of pathways that determine the periodicity of somite formation, rostrocaudal somite polarity and segment identity. Here we use a hypomorphic mutant mouse line to demonstrate that Supt20 (Suppressor of Ty20) is required for development of the axial skeleton. Supt20 hypomorphs display fusions of the ribs and vertebrae at lower thoracic levels along with anterior homeotic transformation of L1 to T14.

Prevention of neural tube defects in Lrp2 mutant mouse embryos by folic acid supplementation.

Background: Neural tube defects (NTDs) are among the most common structural birth defects in humans and are caused by the complex interaction of genetic and environmental factors. Periconceptional supplementation with folic acid can prevent NTDs in both mouse models and human populations. A better understanding of how genes and environmental factors interact is critical toward development of rational strategies to prevent NTDs.

Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures.

Background: Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts.

Abnormal labyrinthine zone in the Hectd1-null placenta.

Introduction: The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta.