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Intellectual and Developmental Disabilities Research Center

Houston, Texas

Intellectual and Developmental Disabilities Research Center
Intellectual and Developmental Disabilities Research Center
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Fragile X Center Project 1

The principal goal of this project is to elucidate the requirements for Fmrp during development. Fragile X syndrome is widely considered to be a developmental disorder; yet direct evidence to support this assertion is limited. We propose to use mouse models that allow expression of Fmrp to be manipulated in a time-dependent manner to assess the requirement for Fmrp during development. Temporal deletion of Fmr1 in mice during embryonic and postnatal development will be achieved by in vivo expression of a Tamoxifen-inducible Cre recombinase to ablate the Fmr1 promoter and first exon flanked by lox P sites. A similar approach will allow restoration of full Fmr1 expression from a gene that has an interfering neomycin cassette in intron 1 that can be removed with Cre recombination. Using these inducible Fmr1 alleles, we will determine whether the phenotypes observed in fragile X mice result from a lack of postnatal FMRP expression or are due to lasting consequences of the absence of FMRP during development.

Relevance of the project to IDDRC mission:

Fragile X syndrome is the leading cause of inherited mental retardation.

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