Mutation of the ectodysplasin-A gene results in bone defects in mice.
Anhidrotic ectodermal dysplasia (EDA) is an X-linked, recessive genetic disease characterized by dysfunctional sweat glands, poorly developed teeth, and premature balding in human beings. This disorder results from mutations in the gene for ectodysplasin-A, a type II transmembrane protein with tumour necrosis factor-alpha domains. An animal model of EDA, the Tabby mouse, also has mutations in the ectodysplasin-A gene and defects similar to those of human beings with EDA. In addition to these defects, Tabby mice acquire deformities in the distal portion of their tails at 10-12 weeks of age. Whole-mount staining of the skeleton with Alizarin Red and Alcian Blue revealed that the tail defect resulted from vertebral fractures just distal to the epiphysis. Histological analysis demonstrated that the structure of both the epiphysis and the subepiphyseal zone of the tail vertebrae was dysplastic while the shaft of the diaphysis was relatively normal. The overall structure of the trabecular bone of these animals was examined through 3-dimensional microcomputed tomography of the tibia. This analysis indicated that Tabby mice had a mild increase in the interconnectivity of the intertwined trabecular bone network but that individual trabeculae were relatively normal. Since it has been determined recently that the ectodysplasin-A gene is expressed in the osteoblasts of developing human embryos, it appears likely that this gene plays a role in normal bone development.
Hill
N L
NL
Department of Biological Sciences, The University of Delaware, Newark, DE 19716, USA.
Laib
A
A
Duncan
M K
MK
D000818:Animals; D001847:Bone Diseases / Q000235:genetics* / Q000473:pathology; D053331:Ectodysplasins; D005260:Female; D006197:Hair / Q000002:abnormalities; D021621:Imaging, Three-Dimensional; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013131:Spine / Q000002:abnormalities*; D013623:Tail / Q000002:abnormalities*; D014057:Tomography, X-Ray Computed
C506018:EDA protein, human; D053331:Ectodysplasins; C506019:Eda protein, mouse; D008565:Membrane Proteins