DCLK1 is one of three doublecortin-like kinases similar to the Ca2+/calmodulin-dependent protein kinase (CaMK) family. DCLK1 mRNA, like that of the homologous DCLK2 and DCLK3, is highly expressed in adult brain, but only DCLK1 and DCLK2 transcripts are present in human fetal brain and the developing mouse embryo, suggesting that DCLK1 and DCLK2 may play roles in cortical development. The DCLK proteins are homologous to Doublecortin (DCX), a gene that is mutated in X-linked human lissencephaly. In mouse models where the DCX gene has been disrupted, DCLK1 expression increases slightly and appears to compensate for the loss of DCX, as mice mutant for both DCX and DCLK1 show a severe phenotype including perinatal lethality, disorganized neocortical layering, and profound hippocampal cytoarchitectural disorganization. Unlike DCLK1, DCLK2 expression does not change in DCX-null mice.
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