International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


TRUNCATION OF LIM HOMEOBOX TRANSCRIPTION FACTOR Lmx1a RESULTS IN ABNORMAL DEVELOMENT OF THE CENTRAL NERVOUS SYSTEM OF qc/qc RAT

Kazuhiro Kitada
Kyoto University
Yoshidakonoe-cho
Sakyo-ku
Kyoto 606-8501
Japan

Co-Authors: 1)Muraguchi T, 2)Ueno M, 2)Kuwamura M, 3)Guénet JL, 1)Serikawa T
Institutions: 1) Institute of Laboratory Animals, Kyoto University, 2)College of Agriculture, Osaka Prefecture University, 3)Unité de Génétique des Mammiferes, Institut Pasteur

The qc (queue courte) rat mutation was found in the ACI/Pas stock owing to its short tail. Homozygotes also exhibit a circling behavior. The main pathological changes in the CNS are hypoplasia of the cerebellum and hippocampus as well as maldeveloped corpus callosum and choroid plexus. These phenotypes are inherited as an autosomal recessive trait, and the causative gene qc was mapped to rat Chr 13. Interestingly, the segment where the qc locus was assigned shows homology with mouse Chr 1, the region of which includes the dreher (dr) locus. The mutation dr causes a phenotype similar to the one in qc rat. In the mouse the dr gene was recently identified as Lmx1a, a LIM homeobox gene that is expressed in the roof plate along the neuraxis. Isolating the orthologous gene in qc rats, we found that the LIM encoding gene was truncated. By this truncation, its homeobox domain was deleted, resulting in a loss-of-function allele. Moreover analysis for the normal expression pattern showed that Lmx1a was expressed in the CNS not only in embryonic stages, but also in postnatal stages, corresponding to architectural development of the cerebral cortex and cerebellum. Our study supported the hypothesis that Lmx1a plays a crucial role for normal development of the CNS throughout all stages, perhaps via regulation of its downstream molecules such as diffusible signaling molecules or trophic factors.


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