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KS Wang, PA Grimes, DE Stambolian; Characterization and Localization of the Tcm Mouse Mutation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):482.
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Purpose:Tcm (total cataract with microphthalmia) is an X-irradiation induced autosomal dominant mouse mutation. In this study, we report on the histopathology of the Tcm homozygous mouse. We also present gene mapping data that further localizes the Tcm gene on mouse chromosome 4. Methods:E13 embryos and brains of P1, P10, and adult mice were fixed in 4% paraformaldehyde, 0.1 M phosphate buffer. E13 embryos were embedded in Historesin. Brains were embedded in paraffin. Specimens were serially sectioned at 6µm and stained with hematoxylin and eosin using standard methods for light microscopic examination. Genomic DNA was prepared from normal and homozygous Tcm mouse. Following agarose gel electrophoresis and Southern blotting, blots were hybridized with probes for candidate genes mapping to the Tcm locus. Results:Adult Tcm homozygous mice are uniformly anophthalmic. A variable number of Tcm mice also display a domed skull, hunched back and malocclusion of incisors. Day E13 homozygous mice show a failure in ventral patterning of the optic cup. In addition the optic stalk remains patent and lined with what appear to be embryonic retinal cells. A number of defects have also been seen in Tcm mouse brains of different ages. These abnormalities are variable and include possible hydrocephalus, cerebellar defects, white matter cysts, and absence of the septum pellucidum. Known mouse genes that localize near the defined Tcm locus have been identified as candidate genes. A genomic rearrangement has been identified in the Tcm homozygous mouse by Southern blot analysis when probed with the candidate gene Cbfa2t1h. Conclusion:Histological analysis of the Tcm mouse suggests severe abnormalities occur during development that may involve axis patterning of the eye and/or brain. Further characterization of the homozygous Tcm phenotype will be conducted, with plans for detailed evaluation of eye and brain histopathology at different stages in development. The genomic rearrangement seen in the Tcm mouse by Southern blot may indicate that the Tcm defect resides within the vicinity of the Cbfat21h gene.
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