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Science 23 June 2000:
Vol. 288. no. 5474, pp. 2226 - 2230
DOI: 10.1126/science.288.5474.2226
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Reports

Impaired Cued and Contextual Memory in NPAS2-Deficient Mice

Joseph A. Garcia, 12 Di Zhang, 12 Sandi Jo Estill, 1 Carolyn Michnoff, 1 Jared Rutter, 1 Martin Reick, 1 Kristin Scott, 3 Ramon Diaz-Arrastia, 3 Steven L. McKnight 1*

Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain. Targeted insertion of a beta -galactosidase reporter gene (lacZ) resulted in the production of an NPAS2-lacZ fusion protein and an altered form of NPAS2 lacking the bHLH domain. The neuroanatomical expression pattern of NPAS2-lacZ was temporally and spatially coincident with formation of the mature frontal association/limbic forebrain pathway. NPAS2-deficient mice were subjected to a series of behavioral tests and were found to exhibit deficits in the long-term memory arm of the cued and contextual fear task. Thus, NPAS2 may serve a dedicated regulatory role in the acquisition of specific types of memory.

1 Department of Biochemistry,
2 Department of Internal Medicine, Molecular Cardiology Division,
3 Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
*   To whom correspondence should be addressed. E-mail: steven.mcknight{at}utsouthwestern.edu

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