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.

Fmr1, Fmrp function, Purkinje neuron
dx.doi.org/10.1016/j.nbd.2005.08.019, hdl.handle.net/1765/62879
Neurobiology of Disease
Department of Clinical Genetics

Mientjes, E.J, Oostra, B.A, Nieuwenhuizen, I.M, Kirkpatrick, L.L, Zu, T, Hoogeveen-Westerveld, M, … Nelson, D.L. (2006). The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo. Neurobiology of Disease, 21(3), 549–555. doi:10.1016/j.nbd.2005.08.019