title: Pax3, neural crest and cardiovascular development.
abstract: The understanding of cardiovascular development has begun a transformation from the descriptive science of anatomy and embryology to a molecular understanding of the cellular and subcellular events leading to proper cardiac morphogenesis. Powerful tools available to molecular geneticists have identified numerous examples of specific gene defects that result in predictable cardiovascular abnormalities. Not only have certain genes been "knocked out" (mutated by homologous recombination in embryonic stem cells), but also single gene defects have been found to underlie the cardiovascular derangements observed in certain inbred mouse lines. Such is the case for the mouse mutant Splotch, which was first described in 1954 as a spontaneously occurring mutation resulting in a white belly spot. More recently, the genetic defect of all of the various Splotch alleles has been found to be due to mutations or deletions of a gene called Pax-3. In the homozygous state, these mutations result in embryonic lethality at about day 13.5 of mouse embryogenesis (E13.5). These embryos display abnormalities strikingly reminiscent of human DiGeorge syndrome. These include outflow tract abnormalities of the heart, such as double-outlet right ventricle (DORV) and persistent truncus arteriosus (PTA), as well as abnormalities of the great vessels and the thyroid and parathyroid glands. These defects suggest an underlying abnormality of neural crest, including its contribution to the cardiovascular system. © 1996, Elsevier Science Inc. (Trends Cardiovasc Med 1996;6:255-261).
authors.affiliation: Jonathan A. Epstein is at the Division of Cardiology, Hospital of the University of Pennsylvania,Philadelphia, PA 19104,USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Epstein