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Cognitive and sensorimotor gating impairments in transgenic mice overexpressing the schizophrenia susceptibility gene Tcf4 in the brain


, : Cognitive and sensorimotor gating impairments in transgenic mice overexpressing the schizophrenia susceptibility gene Tcf4 in the brain. Biological Psychiatry 68(1): 33-40

The combined analysis of several large genome-wide association studies identified the basic helix-loop-helix (bHLH) transcription factor TCF4 as one of the most significant schizophrenia susceptibility genes. Its function in the adult brain, however, is not known. TCF4 belongs to the E-protein subfamily known to be involved in neurodevelopment. The messenger RNA expression of Tcf4 is sustained in the adult mouse brain, suggesting a function in the adult nervous system. Tcf4 null mutant mice die perinatally, and haploinsufficiency of TCF4 in humans causes severe mental retardation. To investigate the possible function of TCF4 in the adult central nervous system, we generated transgenic mice that moderately overexpress TCF4 postnatally in the brain to reduce the risk of developmental effects possibly interfering with adult brain functions. Tcf4 transgenic mice were characterized with molecular, histological, and behavioral methods. Tcf4 transgenic mice display profound deficits in contextual and cued fear conditioning and sensorimotor gating. Furthermore, we show that TCF4 interacts with the neurogenic bHLH factors NEUROD and NDRF in vivo. Molecular analyses revealed the dynamic circadian deregulation of neuronal bHLH factors in the adult hippocampus. We conclude that TCF4 likely acts in concert with other neuronal bHLH transcription factors contributing to higher-order cognitive processing. Moderate transcriptional deregulation of Tcf4 in the brain interferes with cognitive functions and might alter circadian processes in mice. These observations provide insight for the first time into the physiological function of TCF4 in the adult brain and its possible contributions to neuropsychiatric disease conditions.

US$19.90

PMID: 20434134

DOI: 10.1016/j.biopsych.2010.03.015


Other references

Han, S.; Speich, J.E.; Eddinger, T.J.; Berg, K.M.; Miner, A.S.; Call, C.; Ratz, P.H., 2006: Evidence for absence of latch-bridge formation in muscular saphenous arteries. Large-diameter elastic arteries can produce strong contractions indefinitely at a high-energy economy by the formation of latch bridges. Whether downstream blood vessels also use latch bridges remains unknown. The zero-pressure medial thickness an...

Lockie, S.; Lyons, K.; Lawrence, G., 2000: Constructing green foods: corporate capital, risk, and organic farming in Australia and New Zealand. Public concern over environmental quality and food safety has culminated in the development of markets for "green" foods - foods that are variously construed as fresh, chemical-free, nutritious, natural, or produced in an environmentally...

Ronov A.B., 1972: Composition evolution in rocks and geochemical processes in the sedimentary shell of the Earth. English translation of Russian article, see Geokhimiya No. 2, 1972.

Greene, T.; Kanagasundaram, N.; Larive, B.; Paganini, E.P., 2002: Unified quantification of hemodialysis dose in non-steady state conditions of acute renal failure. Journal of the American Society of Nephrology 13(Program and Abstracts Issue): 237A, September

Romanova, EP., 1985: The role of zooplankton in the processes of self purification in Kujbyshev Reservoir.. Trudy Instituta Biologii Vnutrennikh Vod, 5255: 69-79

McKee, M.; Priest, P.; Ginzler, M.; Black, N., 1992: Achieving consensus on out-of-hours laboratory tests. Many reports on guidelines for investigation describe either the guidelines themselves or their implementation. Implicitly these assume that there has been general agreement about the guidelines, whereas there may be uncertainty about the appropri...

Jeunet, F., 1965: Thymoma and immunoglobin deficiency syndrome. Schweizerische Medizinische Wochenschrift 95(43): 1419-1420

Shrimpton, E.A.G., 1940: The error of vitamin D assay by the ash content of bone method. Results obtained by Kon in estimating biologically the vitamin D of butters at different seasons of the year with percentage bone ash as criterion, were analysed statistically, and it was found that the curve relating response to dose was logarith...

Dean, J.B.; Huang, R.Q.; Fyffe, R.E.W., 1995: Anatomically coupled CO-2/H+-chemosensitive neurons in the dorsal medulla. Society for Neuroscience Abstracts 21(1-3): 1883

Bezzi, M., 1920: Nota sul genere Crypto chaetum con descrizione di una nuova specie delle Filippine. Atti della Societa Italiana di Scienze Naturali Pavia, 58 237-252