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Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Fmr1 knockout mouse has a distinctive strain-specific learning impairment
1Department of Genetics, NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, NY 10314, Staten Island, USA. Dobby@webspan.net
Abstract:
The Fmr1 gene knockout mouse is a model for the human Fragile X mental retardation syndrome. Fmr1 knockout mice with a C57BL/6-129/OlaHsd hybrid background have been reported to have only a very mild deficiency in learning the 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 maze 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 the 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 learning a specific visuospatial task in FVB/N-129 hybrid mice but not in C57BL/6 mice. The strain dependence may model the influence of genetic background in the human Fragile X syndrome.
Insights
Fmr1 gene knockout mice show learning deficits in a visuospatial task, but this depends on their genetic background. This strain-specific effect may reflect genetic influences in human Fragile X syndrome.
Area of Science:
- Neuroscience
- Genetics
- Behavioral Science
Background:
- The Fmr1 gene knockout mouse serves as a model for human Fragile X mental retardation syndrome.
- Previous studies indicated mild learning deficiencies in C57BL/6-129/OlaHsd hybrid Fmr1 knockout mice.
Purpose of the Study:
- To investigate the impact of the Fmr1 gene knockout on learning and memory in different mouse genetic backgrounds.
- To determine if the genetic background influences the manifestation of learning deficits in Fmr1 knockout mice.
Main Methods:
- Comparison of Fmr1 knockout mice and wild-type littermates on a cross-shaped water maze task.
- Testing mice with either an FVB/N-129/OlaHsd hybrid background or a C57BL/6 background.
- Assessment of fear conditioning to evaluate general learning and memory.
Main Results:
- FVB/N-129 hybrid Fmr1 knockout mice exhibited significant deficits in learning the water maze task compared to controls.
- C57BL/6 background Fmr1 knockout mice showed no significant learning impairment in the water maze.
- No differences in fear conditioning were observed between knockout and normal mice in either background.
Conclusions:
- The Fmr1 gene knockout impairs visuospatial learning in a manner dependent on the mouse genetic background.
- The observed strain dependence highlights the role of genetic background in modulating Fragile X syndrome phenotypes.
- These findings suggest that mouse models need careful consideration of genetic background for accurate translation to human conditions.
