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Expression changes of microtubule associated protein 1B in the brain of Fmr1 knockout mice
Zhao-Xia Wei1, Yong-Hong Yi, Wei-Wen Sun
1Neurology Department of the Second Affiliated Hospital and Institute of Neuroscience of Guangzhou Medical College, Guangzhou, China.
Objective:
To explore the regulatory effect of fragile X mental retardation protein (FMRP) on the translation of microtubule associated protein 1B (MAP1B).
Methods:
The expressions of MAP1B protein and MAP1B mRNA in the brains of 1-week and 6-week old fragile X mental retardation-1 (Fmr1) knockout (KO) mice were investigated by immunohistochemistry, Western blot, and in situ hybridization, with the age-matched wild type mice (WT) as controls.
Results:
The mean optical density (MOD) of MAP1B was significantly decreased in each brain region in KO6W compared with WT6W, whereas in KO1W, this decrease was only found in the hippocampus and cerebellum. MAP1B in 6-week mice was much less than that in 1-week mice of the same genotype. The results of Western blot and in situ hybridization showed that MAP1B protein and MAP1B mRNA were significantly decreased in the hippocampus of both KO1W and KO6W.
Conclusion:
The decreased MAP1B protein and MAP1B mRNA in the Fmr1 knockout mice indicate that FMRP may positively regulate the expression of MAP1B.
Insights
Fragile X mental retardation protein (FMRP) positively regulates microtubule associated protein 1B (MAP1B) expression. FMRP deficiency in knockout mice leads to decreased MAP1B protein and mRNA levels, impacting brain development.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Fragile X syndrome is a genetic disorder associated with intellectual disability.
- Fragile X mental retardation protein (FMRP) plays a crucial role in neuronal development.
- Microtubule associated protein 1B (MAP1B) is essential for neuronal structure and function.
Purpose of the Study:
- To investigate the regulatory role of FMRP in MAP1B translation.
- To determine if FMRP deficiency affects MAP1B expression in the brain.
Main Methods:
- Utilized Fmr1 knockout (KO) and wild-type (WT) mice at 1 and 6 weeks of age.
- Employed immunohistochemistry, Western blot, and in situ hybridization to assess MAP1B protein and mRNA levels.
- Compared gene and protein expression between KO and WT groups across different brain regions and ages.
Main Results:
- Significantly decreased MAP1B protein and mRNA observed in Fmr1 KO mice compared to WT controls.
- MAP1B levels were lower in 6-week-old KO mice across brain regions, and in 1-week-old KO mice in the hippocampus and cerebellum.
- Age-dependent decrease in MAP1B expression was noted in both genotypes.
Conclusions:
- FMRP appears to positively regulate MAP1B expression.
- Reduced MAP1B in Fmr1 KO mice suggests a potential mechanism contributing to fragile X-associated neurodevelopmental deficits.
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