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Brain Res Dev Brain Res. 2005 Mar 31;155(2):99-106.

Mutation at the Lmx1a locus provokes aberrant brain development in the rat.

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Laboratory of Veterinary Pathology, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.


A rat short-tail mutation with neurological defects (named queue courte, qc) was discovered. Histopathology in adult qc/qc rats revealed hypoplasia of the cerebellum and hippocampus, maldevelopment of the choroid plexus and corpus callosum. These abnormalities are strongly reminiscent of the phenotypic abnormalities found in the shaker short-tail or dreher (dr) mouse mutation at the LIM homeobox transcription factor 1 alpha locus (Lmx1a). The qc mutation is an autosomal recessive and has been mapped to the dr homologous region on rat chromosome 13, and Northern blot analysis demonstrated no expression of Lmx1a in qc/qc rats. Narrowing and distortion of the ventricles were observed from embryonic day 17 (E17) in qc/qc rats. From E17, fusion of the opposing neuroepithelium and formation of neuroepithelial rosettes were also found. Arrangements of neuroepithelial cells were disturbed and processes of radial glia were disoriented in the fused lesions. Neuronal migration analysis using BrdU immunohistochemistry revealed defective migration from the neuroepithelium toward the neocortex and mesencephalon in qc/qc rats. These findings suggest that the qc mutation is involved in development of the ventricular system and dorsal migration of neurons.

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