Chapter 3 Murine Models of Holoprosencephaly

摘要: Holoprosencephaly (HPE), the most common developmental defect of forebrain and midface, is caused by a failure to delineate midline in these structures. Both genetic environmental etiologies exist for HPE, clinical presentation highly variable. HPE occurs sporadic inherited forms, even pedigrees characterized incomplete penetrance variable expressivity. Heterozygous mutations eight different genes have been identified human disruption Sonic hedgehog expression and/or signaling rostroventral region embryo major effect mutations. An understanding mechanisms whereby defects teratogenic exposures become manifest as anomalies varying severity requires experimental models that accurately reproduce spectrum seen HPE. The mouse has emerged such model, because its ease manipulation similarity humans development face. generally observed mice homozygous orthologs though, unlike humans, rarely with heterozygous Moreover, reverse genetics provided wealth new candidate genes. Construction hypomorphic alleles, interbreeding produce double mutants, analysis on backgrounds generated multiple begun provide insight into conundrum spectrum. Here, we review an emphasis pathways known be defective describe strengths weaknesses various murine