Understanding doublecortin-like kinase gene function through transgenesis

Doublecortin (DCX) and DCX-domain containing Doublecortin-Like Kinase (DCLK) gene splice variants function during embryonic development, where they play a role in microtubule binding. Although a role for the DCLK gene during embryogenesis is clearly established, it encodes multiple, different transcripts, some of which are expressed in the adult brain or in response to neuronal activity. This suggests that the DCLK gene may have additional functions beyond neuronal development. Strikingly, the roles of two DCLK gene products, DCLK-short and CaMK-related peptide (CARP), remain largely elusive. Therefore, we have generated transgenic mice with over-expression of either CARP or a constitutively active form of DCLK-short, called _C-DCLK-short, in the brain. This has opened up the possibility to study the effect of over-expression of these DCLK transcripts in the brain during adulthood. To gain more insight in DCLK gene function in the adult brain we aimed to study and describe the phenotypes of these transgenic mice at different functional levels, such as the genetic, network and behavioural level