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The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo.

Erasmus MC, CBG Department of Clinical Genetics, Erasmus University, Room Ee971, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Neurobiology of Disease (Impact Factor: 5.2). 04/2006; 21(3):549-55. DOI: 10.1016/j.nbd.2005.08.019
Source: PubMed

ABSTRACT The FMR1 gene, mutated in Fragile X syndrome patients, has been modeled in mice with a neomycin cassette inserted in exon 5 of the mouse Fmr1 gene creating an Fmr1 knockout (Fmr1 KO) allele. This results in animals lacking Fmr1 protein (Fmrp) expression in all tissues. We have created a new, more versatile Fmr1 in vivo KO model (Fmr1 KO2) and generated conditional Fmr1 KO (CKO) mice by flanking the promoter and first exon of Fmr1 with lox P sites. This enables us to create a null allele in specific cell types and at specific time points by crossing Fmr1 CKO mice with tissue specific or inducible cre-recombinase expressing mice. The new Fmr1 KO2 line does not express any Fmrp and also lacks detectable Fmr1 transcripts. Crossing the Fmr1 CKO line with a Purkinje cell-specific cre-recombinase expresser produces mice that are null for Fmr1 in Purkinje neurons but wild type in all other cell types.

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