title: The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo.
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.
authors.affiliation: Erasmus MC, CBG Department of Clinical Genetics, Erasmus University, Room Ee971, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Mientjes
authors.forename: I
authors.initials: I
authors.lastname: Nieuwenhuizen
authors.forename: L
authors.initials: L
authors.lastname: Kirkpatrick
authors.forename: T
authors.initials: T
authors.lastname: Zu
authors.forename: M
authors.initials: M
authors.lastname: Hoogeveen-Westerveld
authors.forename: L
authors.initials: L
authors.lastname: Severijnen
authors.forename: M
authors.initials: M
authors.lastname: Rifé
authors.forename: R
authors.initials: R
authors.lastname: Willemsen
authors.forename: D L
authors.initials: DL
authors.lastname: Nelson
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse