The Doublecortin-Like Kinase (DCLK) gene is involved in neuronal migration during development. Through alternative splicing the DCLK gene also produces a transcript called Ca2+/calmodulin dependent... Show moreThe Doublecortin-Like Kinase (DCLK) gene is involved in neuronal migration during development. Through alternative splicing the DCLK gene also produces a transcript called Ca2+/calmodulin dependent protein kinase (CaMK)-related peptide (CARP) that is expressed exclusively during adulthood in response to neuronal activity. The function of CARP, however, is poorly understood. To study CARP function, we have generated transgenic mice with over-expression of the CARP transcript in, amongst other brain areas, the hippocampus. We aimed to characterize possible behavioral adaptations of these mice by using a Pavlovian fear conditioning approach. This type of fear conditioning, in which both the hippocampus and amygdala are critically involved, allows studying the formation and extinction of fear related memories. We here report on the behavioral adaptations of two distinct transgenic lines: one with high levels of CARP in the hippocampus and amygdala, whilst the other has high levels of CARP in the hippocampal formation, but not in the amygdala. We tested both mouse lines separately by comparing them to their wild-type littermate controls. We provide evidence suggesting consolidation of contextual fear memories is strengthened in mice of both transgenic lines. (C) 2010 Elsevier Inc. All rights reserved. Show less
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... Show moreDoublecortin (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. Show less
