Fmr1 knockout mouse has a distinctive strain-specific learning impairment

The Fmr1 gene knockout mouse is a model for the human Fragile X mental reta rdation syndrome. Fmr1 knockout mice with a C57BL/6-129/OlaHsd hybrid backg round have been reported to have only a very mild deficiency in learning th e Morris water maze task. We compared the effect of this knockout mutation on learning in mice with either an FVB/N-129/OlaHsd hybrid background or a C57BL/6 background. When FVB-129 mice were tested in a cross-shaped water m aze task, the knockout mice showed a pronounced deficiency in their ability to learn the position of a hidden escape platform in comparison to normal littermates. In contrast, knockout mice with a C57BL/6 background learned t he maze just as well as their normal littermates. Fear conditioning did not reveal differences between knockout and normal mice in either background. These results show that silencing the Fmr1 gene clearly interfered with lea rning a specific visuospatial task in FVB/N-129 hybrid mice but not in C57B L/6 mice. The strain dependence may model the influence of genetic backgrou nd in the human Fragile X syndrome. (C) 2000 IBRO. Published by Elsevier Sc ience Ltd. All rights reserved.