EXPRESSION AND CHROMOSOMAL LOCALIZATION OF KIAA0369, A PUTATIVE KINASE STRUCTURALLY RELATED TO DOUBLECORTIN

Neuropathy in vertebrates can be a consequence of failure of genes inv olved in the nervous system to be expressed at the correct times and l evels during embryonic life. Recently, a brain specific gene, Doubleco rtin, was cloned and was shown to have mutations in X-linked Lissencep haly and double cortex syndrome. KIAA0369 is a putative kinase that is structurally related to Doublecortin. We compared the expression of K IAA0369 with that of Doublecortin, both of which were expressed specif ically or predominantly in fetal brain among 20 different tissues exam ined. The deduced products of both genes contain a unique domain (the Doublecortin [DC] domain), but KIAA0369 also contains a calmodulin-dep endent kinase (CaM kinase)-like domain following the DC domain. We fou nd at least four splicing variants of KIAA0369: KIAA0369-AS (type A, s hort version), KIAA0369-AL (type A, long version), KIAA0369-BS (type B , short version), and KIAA0369-BL (type B, long version). KIAA0369-B, which lacked the DC domain and maintained the kinase domain, was expre ssed in adult as well as fetal brain, but the variants that included t he DC domain, KIAA0369-A, were expressed predominantly in fetal brain. These results suggest that the DC domain plays an important role in t he development of the nervous system. In the adult brain, KIAA0369 was expressed in all 15 different regions examined, more intensely in cer ebral cortex, occipital pole, frontal lobe, amygdala, and hippocampus, and less intensely in corpus callosum and thalamus. The murine homolo gs of Doublecortin and KIAA0369 were not detectable in 7-day mouse emb ryos, but both genes were expressed extensively in 11-day embryos. Hum an KIAA0369 was mapped by fluorescence in situ hybridization (FISH) to chromosome 13q13-q14.1. The presence of genes related to neuropathy h as been reported in this locus.