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Expression of the murine homologue of FMR2 in mouse brain and during development
L Chakrabarti1, J Bristulf, G S Foss
1Genetics Unit, Biochemistry Department, Oxford University, South Parks Road, Oxford, OX1 3QU, UK.
Abstract:
The expression of the FRAXE fragile site on the human X chromosome is associated with the expansion of a CCG repeat at the 5' end of the FMR2 gene. The repeat expansion results in transcriptional silencing of the gene and this event has been found to be associated with mild mental handicap in families. We have previously shown that the gene is particularly abundantly expressed in the hippocampus and amygdala by northern analysis. Here we demonstrate the expression pattern of the homologous gene in adult mouse brain and early mouse embryos. High levels of fmr2 mRNA were noted in the hippocampus, the piriform cortex, Purkinje cells and the cingulate gyrus. Expression of fmr2 occurs on, or before, day 7 in the embryo and reaches its highest levels at 10.5-11.5 days. A more detailed analysis shows that the fmr2 expression in the embryo at 11 days is more specific and evident to the roof of the hind brain and the lateral ventricle of the brain. The coding sequence of the mouse fmr2 gene shows very high conservation with 88% amino acid identity to the human FMR2 sequence.
Insights
The FMR2 gene, linked to mild mental handicap via CCG repeat expansion, shows specific expression patterns in adult mouse brains and developing embryos. This research maps its crucial roles in neurological development.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- FRAXE fragile site expansion on the human X chromosome involves CCG repeat expansion in the FMR2 gene.
- This expansion leads to FMR2 gene silencing and is linked to mild mental handicap.
- Previous studies indicated high FMR2 gene expression in the hippocampus and amygdala.
Purpose of the Study:
- To investigate the expression pattern of the homologous fmr2 gene in adult mouse brains.
- To analyze the expression of fmr2 during early mouse embryonic development.
- To understand the conservation of the fmr2 gene sequence between mice and humans.
Main Methods:
- Northern analysis was used to detect fmr2 mRNA levels.
- Expression patterns were analyzed in adult mouse brain regions and at various embryonic stages.
- Sequence analysis was performed to determine amino acid identity between mouse and human FMR2.
Main Results:
- High fmr2 mRNA levels were observed in the adult mouse hippocampus, piriform cortex, Purkinje cells, and cingulate gyrus.
- Embryonic fmr2 expression begins by day 7, peaking at 10.5-11.5 days.
- Specific embryonic expression was noted in the hind brain roof and lateral ventricles at 11 days.
- The mouse fmr2 coding sequence exhibits 88% amino acid identity with the human FMR2 sequence.
Conclusions:
- The fmr2 gene is abundantly expressed in specific regions of the adult mouse brain, particularly areas involved in cognition and emotion.
- Embryonic fmr2 expression is dynamic and localized, suggesting critical roles during early neural development.
- High sequence conservation highlights the functional importance of the FMR2 gene across species.