Mouse mutations that model human craniofacial/limb abnormalities

Baylor College Of Medicine, Houston TX

Investigators

Linked publications & trials

Abstract

Many mouse mutations affect craniofacial structure or limb morphology. Craniofacial mutations can be caused by a variety of defects, including those affecting brain structures, neural crest cell migration, skeletal morphology, tooth and palate development, and nasal and eye morphogenesis. As a result of ongoing mutagenesis experiments in my laboratory, many mutations affecting craniofacial and limb development have been isolated. Some of these appear to be novel mutations, and some could be models of human comparative map locations and phenotypes of dominant mouse mutations will be compared with craniofacial anomalies found in Finnish families. Specifically, we will screen for dominant craniofacial/limb malformations in G1 mice from ongoing ethylnitrosourea (ENU) mutagenesis experiments by examining G1 mice both visually and by X-ray analysis. Second, recessive mutations that model human Meckel Syndrome (Project III) will likely be isolated in a mapped and phenotypically characterized to determine the possibility that they are models of human craniofacial malformations. Some of the mouse mutations that map to the conserved location in humans, and are phenotypically similar, will be analyzed molecularly in parallel with the human disease locus. Of particular interest will be identifying the mouse homologue of the human Meckel syndrome gene. By comparing phenotypes of craniofacial anomalies and human, and improving methods for the detection of these anomalies in collaboration with the Image Analysis Core, we hope to define parameters to better model human disease and to identify similar disease syndromes in the mouse. These objectives will be facilitated in this Program Project by working directly with clinicians.