2007
DOI: 10.1073/pnas.0611003104
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Deletion of CASK in mice is lethal and impairs synaptic function

Abstract: CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca 2؉ /calmodulin-kinase domain, central PDZ and SH3 domains, and a C-terminal guanylate kinase domain. Many potential activities for CASK have been suggested, including functions in scaffolding the synapse, in organizing ion channels, and in regulating neuronal gene transcription. To better define the physiological importance of CASK, we have now analyzed CASK ''knockdown'' mice in which CASK expression was suppressed by Ϸ70%, a… Show more

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Cited by 195 publications
(241 citation statements)
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“…Indeed, CASK has been shown to be important for the trafficking of several proteins, including calcium and potassium channels (Maximov et al, 1999;Leonoudakis et al, 2004). However, when comparing the phenotypes of ␣-Nrxn knockouts (Missler et al, 2003) and null-mutants of CASK, important differences are revealed since the latter displays unchanged evoked neurotransmission (Atasoy et al, 2007). Therefore, although we observed the presence of CASK on Nrxn-positive transport vesicles, consistent with their known interaction (Hata et al, 1996;Mukherjee et al, 2008), CASK is unlikely to be essential for Nrxn trafficking.…”
Section: Discussioncontrasting
confidence: 38%
“…Indeed, CASK has been shown to be important for the trafficking of several proteins, including calcium and potassium channels (Maximov et al, 1999;Leonoudakis et al, 2004). However, when comparing the phenotypes of ␣-Nrxn knockouts (Missler et al, 2003) and null-mutants of CASK, important differences are revealed since the latter displays unchanged evoked neurotransmission (Atasoy et al, 2007). Therefore, although we observed the presence of CASK on Nrxn-positive transport vesicles, consistent with their known interaction (Hata et al, 1996;Mukherjee et al, 2008), CASK is unlikely to be essential for Nrxn trafficking.…”
Section: Discussioncontrasting
confidence: 38%
“…7,[15][16][17] As in humans, Cask is an essential gene in mice because knockout or insertion mutations of Cask in male mice results in neonatal death within 1-2 days after birth. 18,19 Mice carrying the floxed allele of Cask exhibit reduced CASK expression and smaller body size, 18 further suggesting that CASK regulates brain development as well as that of other tissues. Because of lethality and smaller body size, it is either impossible or inappropriate to use knockout or floxed mutant mice to analyze the cognitive functions of CASK.…”
Section: Introductionmentioning
confidence: 99%
“…An additional complication is that these overlapping deficiencies would be predicted to eliminate both the CASK-b and CASK-a isoforms, making it impossible to assign function to a specific form of the protein. To date, however, this null model has been the best available, as disrupting CASK in other species (i.e., mammals) appears to be lethal (Atasoy et al 2007).…”
mentioning
confidence: 99%