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

TitleThe generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo.
Publication TypeJournal Article
Year of Publication2006
AuthorsMientjes, EJ, Nieuwenhuizen, I, Kirkpatrick, L, Zu, T, Hoogeveen-Westerveld, M, Severijnen, L, Rifé, M, Willemsen, R, Nelson, DL, Oostra, BA
JournalNeurobiol Dis
Volume21
Issue3
Pagination549-55
Date Published2006 Mar
ISSN0969-9961
KeywordsAnimals, Blotting, Western, Disease Models, Animal, Fragile X Mental Retardation Protein, Fragile X Syndrome, Immunohistochemistry, Mice, Mice, Knockout, Purkinje Cells, Reverse Transcriptase Polymerase Chain Reaction
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.

DOI10.1016/j.nbd.2005.08.019
Alternate JournalNeurobiol. Dis.
PubMed ID16257225
Grant ListHD024064 / HD / NICHD NIH HHS / United States
HD29256 / HD / NICHD NIH HHS / United States
R01 HD38038 / HD / NICHD NIH HHS / United States