Abstract:

Lafora's disease, an autosomal recessive progressive myoclonus epilepsy, is caused by mutations in the EPM2A gene encoding a dual-specificity phosphatase (DSP) named laforin. Here, we analyzed the developmental and regional expression of murine Epm2a and discussed its evolutionary conservation. A phylogenetic analysis indicated that laforin is evolutionarily distant from other DSPs. Southern zoo blot analysis suggested that conservation of Epm2a gene is limited to mammals. Laforin orthologs (human, mouse, and rat) display more than 94% similarity. All missense mutations known in Lafora disease patients affect conserved residues, suggesting that they may be essential for laforin's function. Epm2a is expressed widely in various organs but not homogeneously in brain. The levels of Epm2a transcripts in mice brains increase postnatally, attaining its highest level in adults. The most intense signal was detected in the cerebellum, hippocampus, cerebral cortex, and the olfactory bulb. Our results suggest that Epm2a is functionally conserved in mammals and is involved in growth and maturation of neural networks. Copyright 2001 Academic Press.

Keywords: Laforin; Lafora'; s disease; epilepsy; dual-specificity phosphatase; homologue; expression; conservation; evolution

Language: English

Document Type: Research article

Affiliations: 1: Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Saitama, 351-0198, Japan 2: Comprehensive Epilepsy Program, VA GLAHS West Los Angeles Medical Center, Los Angeles, California