Research Article

Gene expression profiles in the cerebellum of transgenic mice over expressing the human FMR1 gene with CGG repeats in the normal range

Abstract

Modifications in the GABA pathway are considered to be responsible for motor alterations in animal models for fragile X-associated tremor ataxia syndrome. We analyzed the expression profile in the cerebellum in a transgenic mouse model that over expresses the human FMR1 gene with CGG repeats in the normal range. We used the “GeneChip Mouse Gene 1.0 ST Array” from Affymetrix analyzing 28,853 well-described and -characterized genes. Based on data from the comparative analysis of the expression profile, we detected a significant gradient with a P value GabarapL2, no changes in expression of genes from the GABA pathway were observed, which may explain the absence of an altered motor phenotype in these mice. These results further support the view that toxic effects in fragile X-associated tremor ataxia syndrome are due to expansion of CGG repeats rather than increased mRNA levels, since in the transgenic mice the FMR1 mRNA levels were increased 20-100 times compared with those of control littermates.

Modifications in the GABA pathway are considered to be responsible for motor alterations in animal models for fragile X-associated tremor ataxia syndrome. We analyzed the expression profile in the cerebellum in a transgenic mouse model that over expresses the human FMR1 gene with CGG repeats in the normal range. We used the “GeneChip Mouse Gene 1.0 ST Array” from Affymetrix analyzing 28,853 well-described and -characterized genes. Based on data from the comparative analysis of the expression profile, we detected a significant gradient with a P value GabarapL2, no changes in expression of genes from the GABA pathway were observed, which may explain the absence of an altered motor phenotype in these mice. These results further support the view that toxic effects in fragile X-associated tremor ataxia syndrome are due to expansion of CGG repeats rather than increased mRNA levels, since in the transgenic mice the FMR1 mRNA levels were increased 20-100 times compared with those of control littermates.