Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired-pulse facilitation.
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.
Matilla
A
A
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Roberson
E D
ED
Banfi
S
S
Morales
J
J
Armstrong
D L
DL
Burright
E N
EN
Orr
H T
HT
Sweatt
J D
JD
Zoghbi
H Y
HY
Matzuk
M M
MM
D000704:Analysis of Variance; D000818:Animals; D001259:Ataxia / Q000503:physiopathology; D000067696:Ataxin-1; D000067528:Ataxins; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007859:Learning Disabilities / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency*; D012399:Rotation
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins