CASK-interacting nucleosome assembly protein (CINAP) has been shown to interact with the calcium/calmodulin-dependent serine kinase (CASK) and the T-box transcription factor T-brain-1 (Tbr1) thus modulating the expression of N-methyl-D-aspartic acid receptor subunit 2b (NMDAR2b) in cultured hippocampal neurons. To explore the physiological significance of CINAP in vivo, CINAP knockout mice were generated and subjected to biochemical, anatomical, and behavioral analyses. Unexpectedly, CINAP deletion did not impact NMDAR2b expression, and these CINAP knockout mice were consistently comparable to wild-type littermates in terms of immediate memory (assessed with the Y maze) and associative memory (evaluated by conditioned taste aversion and contextual and auditory fear conditioning). Although CINAP deletion did not obviously influence learning and memory behaviors, CINAP knockout mice exhibited higher locomotor and exploratory activities. Compared with wild-type littermates, the horizontal and vertical movements of the CINAP knockout mice were higher in a novel environment; in home cages, rearing, sniffing, and jumping also occurred more frequently in CINAP knockout mice. These observations suggest that although CINAP deletion in mice does not influence learning and memory behaviors, CINAP is required for restriction of locomotor and exploratory activities.
© 2011 S. Karger AG, Basel
- Cognitive impairment
- N-methyl-D-aspartic acid receptor subunit 2b
- Nucleosome assembly protein
- Hackett A, Tarpey PS, Licata A, Cox J, Whibley A, Boyle J, Rogers C, Grigg J, Partington M, Stevenson RE, Tolmie J, Yates JR, Turner G, Wilson M, Futreal AP, Corbett M, Shaw M, Gecz J, Raymond FL, Stratton MR, Schwartz CE, Abidi FE: CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes. Eur J Hum Genet 2010;18:544–552.
- Tarpey PS, Smith R, Pleasance E, et al: A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet 2009;41:535–543.
- Piluso G, D’Amico F, Saccone V, Bismuto E, Rotundo IL, Di Domenico M, Aurino S, Schwartz CE, Neri G, Nigro V: A missense mutation in CASK causes FG syndrome in an Italian family. Am J Hum Genet 2009;84:162–177.
- Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K: Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet 2008;40:1065–1067.
- Atasoy D, Schoch S, Ho A, Nadasy KA, Liu X, Zhang W, Mukherjee K, Nosyreva ED, Fernandez-Chacon R, Missler M, Kavalali ET, Sudhof TC: Deletion of CASK in mice is lethal and impairs synaptic function. Proc Natl Acad Sci USA 2007;104:2525–2530.
- Hsueh YP: Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol 2009;66:438–443.
- Hsueh YP: The role of the MAGUK protein CASK in neural development and synaptic function. Curr Med Chem 2006;13:1915–1927.
- Hsueh YP, Wang TF, Yang FC, Sheng M: Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/lin-2. Nature 2000;404:298–302.
- Wang GS, Hong CJ, Yen TY, Huang HY, Ou Y, Huang TN, Jung WG, Kuo TY, Sheng M, Wang TF, Hsueh YP: Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron 2004;42:113–128.
- Kuo TY, Hong CJ, Chien HL, Hsueh YP: X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth. J Neurosci Res 2010;88:2364–2373.
- Ozbun LL, You L, Kiang S, Angdisen J, Martinez A, Jakowlew SB: Identification of differentially expressed nucleolar TGF-beta1 target (DENTT) in human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily. Genomics 2001;73:179–193.
- Chai Z, Sarcevic B, Mawson A, Toh BH: Set-related cell division autoantigen-1 (CDA1) arrests cell growth. J Biol Chem 2001;276:33665–33674.
- Wang TF, Ding CN, Wang GS, Luo SC, Lin YL, Ruan Y, Hevner R, Rubenstein JL, Hsueh YP: Identification of TBR-1/CASK complex target genes in neurons. J Neurochem 2004;91:1483–1492.
- Liu P, Jenkins NA, Copeland NG: A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res 2003;13:476–484.
- Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, Alt FW, Westphal H: Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci USA 1996;93:5860–5865.
- Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, Stewart AF, Dymecki SM: High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 2000;25:139–140.
- Lin CW, Huang TN, Wang GS, Kuo TY, Yen TY, Hsueh YP: Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly protein in mouse brain. J Comp Neurol 2006;494:606–619.
- Williams K, Russell SL, Shen YM, Molinoff PB: Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron 1993;10:267–278.
- Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH: Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994;12:529–540.
- Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY: Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994;368:144–147.
- Steele AD, Jackson WS, King OD, Lindquist S: The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington’s and prion diseases. Proc Natl Acad Sci USA 2007;104:1983–1988.
- Annunziata I, Lanzara C, Conte I, Zullo A, Ventruto V, Rinaldi MM, D’Urso M, Casari G, Ciccodicola A, Miano MG: Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation. Am J Med Genet A 2003;118A:217–222.
- Park YJ, Luger K: Structure and function of nucleosome assembly proteins. Biochem Cell Biol 2006;84:549–558.
- Eitoku M, Sato L, Senda T, Horikoshi M: Histone chaperones: 30 years from isolation to elucidation of the mechanisms of nucleosome assembly and disassembly. Cell Mol Life Sci 2008;65:414–444.
- Huang TN, Hsueh YP: CASK point mutation regulates protein-protein interactions and Nr2b promoter activity. Biochem Biophys Res Commun 2009;382:219–222.
- Huang TN, Chang HP, Hsueh YP: CASK phosphorylation by PKA regulates the protein-protein interactions of CASK and expression of the NMDAR2b gene. J Neurochem 2010;112:1562–1573.
- Mignogna P, Viggiano D: Brain distribution of genes related to changes in locomotor activity. Physiol Behav 2010;99:618–626.
- Lukaszewska I, Korczynski R, Markowska A, Kostarczyk E: Emotionality and exploratory behavior following cortico-basomedial amygdala lesion in rat. Acta Neurobiol Exp (Wars) 1980;40:911–932.
- Hashimoto H, Shintani N, Tanaka K, Mori W, Hirose M, Matsuda T, Sakaue M, Miyazaki J, Niwa H, Tashiro F, Yamamoto K, Koga K, Tomimoto S, Kunugi A, Suetake S, Baba A: Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci USA 2001;98:13355–13360.
- Norrholm SD, Das M, Legradi G: Behavioral effects of local microinfusion of pituitary adenylate cyclase activating polypeptide (PACAP) into the paraventricular nucleus of the hypothalamus (PVN). Regul Pept 2005;128:33–41.
- Li Q, Holmes A, Ma L, Van de Kar LD, Garcia F, Murphy DL: Medial hypothalamic 5-hydroxytryptamine (5-HT)1a receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1a sequences. J Neurosci 2004;24:10868–10877.
- Swanson LW: Cerebral hemisphere regulation of motivated behavior. Brain Res 2000;886:113–164.
- Aizawa H, Sato Y, Maekawa M, Fujisawa H, Hirata T, Yuasa S: Development of the amygdalohypothalamic projection in the mouse embryonic forebrain. Anat Embryol (Berl) 2004;208:249–264.
- Kandalaft LE, Zudaire E, Portal-Nunez S, Cuttitta F, Jakowlew SB: Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) exhibits an inhibitory role on tumorigenesis. Carcinogenesis 2008;29:1282–1289.
- Pham Y, Tu Y, Wu T, Allen TJ, Calkin AC, Watson AM, Li J, Jandeleit-Dahm KA, Toh BH, Cao Z, Cooper ME, Chai Z: Cell division autoantigen 1 plays a profibrotic role by modulating downstream signalling of TGF-beta in a murine diabetic model of atherosclerosis. Diabetologia 2010;53:170–179.
- Tu Y, Wu W, Wu T, Cao Z, Wilkins R, Toh BH, Cooper ME, Chai Z: Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. J Biol Chem 2007;282:11722–11731.
Dr. Yi-Ping Hsueh
Institute of Molecular Biology, Academia Sinica
128, Academia Rd., Section 2
Taipei 115, Taiwan (ROC)
Tel. +886 2 278 99311, E-Mail email@example.com
Received: January 17, 2011
Accepted: March 22, 2011
Published online: May 13, 2011
Number of Print Pages : 14
Number of Figures : 9, Number of Tables : 0, Number of References : 36
Vol. 19, No. 3, Year 2011 (Cover Date: August 2011)
Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)
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