Regional and developmental expression of Epm2a gene and its evolutionary conservation

Lafora's disease, an autosomal recessive progressive myoclonus epilepsy, is caused by mutations in the EPM2A gene encoding a dual-specificity phosphat ase (DSP) named laforin, Here, we analyzed the developmental and regional e xpression of murine Epm2a and discussed its evolutionary conservation. A ph ylogenetic analysis indicated that laforin is evolutionarily distant from o ther DSPs, Southern zoo blot analysis suggested that conservation of Epm2a gene is limited to mammals. Laforin orthologs (human, mouse, and rat) displ ay 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 inc rease postnatally, attaining its highest level in adults. The most intense signal was detected in the cerebellum, hippocampus, cerebral cortex, and th e olfactory bulb. Our results suggest that Epm2a is functionally conserved in mammals and is involved in growth and maturation of neural networks. (C) 2001 Academic Press.