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Neurobiol Dis. 2006 Mar;21(3):549-55. Epub 2005 Oct 26.

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

Author information

1
Erasmus MC, CBG Department of Clinical Genetics, Erasmus University, Room Ee971, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.

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.

PMID:
16257225
DOI:
10.1016/j.nbd.2005.08.019
[Indexed for MEDLINE]

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