Mice Lacking Ataxin-1 Display Learning Deficits and Decreased Hippocampal Paired-pulse Facilitation

Overview

Journal J Neurosci

Specialty Neurology

Date 1998 Jul 3

PMID 9651231

Citations 79

Authors

A Matilla

E D Roberson

S Banfi

J Morales

D L Armstrong

E N Burright

H T Orr

J D Sweatt

H Y Zoghbi

M M Matzuk

Affiliations

Soon will be listed here.

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the function of the SCA1 gene product ataxin-1, a novel protein without homology to previously described proteins, we generated mice with a targeted deletion in the murine Sca1 gene. Mice lacking ataxin-1 are viable, fertile, and do not show any evidence of ataxia or neurodegeneration. However, Sca1 null mice demonstrate decreased exploratory behavior, pronounced deficits in the spatial version of the Morris water maze test, and impaired performance on the rotating rod apparatus. Furthermore, neurophysiological studies performed in area CA1 of the hippocampus reveal decreased paired-pulse facilitation in Sca1 null mice, whereas long-term and post-tetanic potentiations are normal. These findings demonstrate that SCA1 is not caused by loss of function of ataxin-1 and point to the possible role of ataxin-1 in learning and memory.

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