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Fragile x mental retardation (Fmr-1) gene expression is down regulated in brain of mice during aging

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Abstract

Fragile x syndrome (FXS) is the most common form of inherited mental retardation disease. This is caused due to expansion of CGG triplet in 5′-untranslated region of fragile x mental retardation 1 (FMR-1) gene. In most of the cases, abnormally large size of the CGG repeat (>200) undergoes hypermethylation, which in turn silences the FMR-1 gene causing thereby complete lack of its protein product called fragile x mental retardation protein (FMRP). Lack of FMRP due to gene silencing or production of faulty protein due to point mutation in KH2 domain of FMRP alters the translational process in neurons and leads to expression of mental retardation phenotype on the patients. The FMRP is expressed ubiquitously in all tissues; however, it is predominantly expressed in neurons and testis. It possesses heterogeneity and is found in many isoforms due to alternative splicing of the FMR-1 transcript. Based on our data from the Western-, slot-, Northern blotting and immunohistochemical studies, we report here the down regulation of Fmr-1 gene and FMRP in mice brain in age-dependent manner. The present finding is important in respect to FMRP-dependent various brain functions i.e., learning, memory, cognition etc. that decrease with advancing age.

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Acknowledgement

The authors acknowledge Prof. MS Kanungo and Prof. MK Thakur for providing support and thank Profs. EW Khandjian, Canada, U Fischer, Germany and J-L Mandel, France for donating anti-FMRP antibody. The financial assistance from CAS in Zoology, Banaras Hindu University is gratefully acknowledged.

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  1. Biochemistry and Molecular Biology laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India

    Kanchan Singh, Pankaj Gaur & S. Prasad

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  1. Kanchan Singh
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  2. Pankaj Gaur
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  3. S. Prasad
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Correspondence to S. Prasad.

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Singh, K., Gaur, P. & Prasad, S. Fragile x mental retardation (Fmr-1) gene expression is down regulated in brain of mice during aging. Mol Biol Rep 34, 173–181 (2007). https://doi.org/10.1007/s11033-006-9032-8

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  • DOI: https://doi.org/10.1007/s11033-006-9032-8

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