The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo.
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.
Mientjes
E J
EJ
Erasmus MC, CBG Department of Clinical Genetics, Erasmus University, Room Ee971, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Nieuwenhuizen
I
I
Kirkpatrick
L
L
Zu
T
T
Hoogeveen-Westerveld
M
M
Severijnen
L
L
Rifé
M
M
Willemsen
R
R
Nelson
D L
DL
Oostra
B A
BA
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
D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse