B6;129-Fzd4^tm2.1Nat/J

Stock number: 011078
Research areas: Cardiovascular Research, Research Tools, Sensorineural Research

Description

This strain combines a conditional knockout and a alkaline phosphatase (AP) reporter of the frizzled 4 (Fzd4; Fz4) gene. Following cre-mediated recombination, the coding region is excised, and the downstream AP reporter is expressed under the control of the Fzd4 promoter in a cell/tissue-specific manner.

Detailed description

This strain combines a conditional knockout and an alkaline phosphatase (AP) reporter of the frizzled 4 (Fzd4; Fz4) gene. LoxP sites flank the 5' and 3' UTR's. Without recombination, homozygotes of this allele are indistinguishable from wild type mice and the AP reporter is not expressed. Following cre-mediated recombination, the coding region is excised, and the downstream AP reporter is expressed under the control of the Fzd4 promoter in a cell/tissue-specific manner. Loss of Fzd4 signaling causes defective vascular growth which leads to chronic but reversible silencing of retinal neurons. Loss of expression in all endothelial cells disrupts the blood brain barrier in the cerebellum. This strain may be useful in studies of vascular growth, remodeling, maintenance and disease.

Development

LoxP sites are inserted before the start codon, and after the 3'UTR. The coding sequence of human placenta alkaline phosphatase gene and rabbit beta-globin 3' UTR were inserted downstream the 3' LoxP site. The mutation was created in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells and the strain was maintained on a mixed C57BL/6 and 129 background by the donating laboratory.

Allele

Symbol: Fzd4^tm2.1Nat
Name: targeted mutation 2.1, Jeremy Nathans
MGI accession ID: MGI:4412057
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Fzd4
Marker name: frizzled class receptor 4
Chromosome: 7
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: One loxP site was inserted in the 5' UTR and another was inserted 3' of the 3' UTR. An alkaline phosphatase sequence was inserted 3' of the last loxP site and was followed by an frt flanked PGK-neo cassette. Flp recombinase expression resulted in the excision of the PGK-neo cassette.