B6N.Cg-Adgrf5^tm1.1Bstc/J

Stock number: 022505
Research areas: Developmental Biology Research, Internal/Organ Research, Research Tools

Description

These Gpr116^flox mutant mice possess loxP sites flanking exon 2 of the targeted gene. This strain may be useful for studying the role of GPR116 in lung surfactant homeostasis.

Detailed description

These Gpr116^flox mutant mice possess loxP sites flanking exon 2, encoding the start codon, of the G protein-coupled receptor 116 (Gpr116). GPR116 is an endothelial cell specific transmembrane receptor. In addition to its pan endothelial expression Gpr116 is also expressed in lung Alveolar Type II cells where it plays a critical role in lung surfactant homeostasis. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.

For example, when bred to B6.Cg-Tg(Tek-cre)12Flv/J mice (Stock No. 004128) expressing Cre recombinase in endothelial cells, resulting offspring display labored breathing by 4 months of age, weigh less than littermates by 14 months, and have a shortened lifespan. They also have an accumulation of surfactant proteins in their lungs, and bronchoalveolar lavage fluid (BALF) has a milky appearance.

When bred to B6.Cg-Tg(SFTPC-rtTA)5Jaw/J and B6.Cg-Tg(tetO-cre)1Jaw/J mice (Stock No. 006235 and Stock No. 006234, respectively) express Cre recombinase in the developing and adult lung and respiratory epithelium, in the resulting doxycycline-treated offspring BALF has increased levels of surfactant proteins, cholesterol and phosphatidylcholine.

Development

A targeting vector was designed to insert a loxP site upstream of exon 2, and a frt-flanked and loxP-flanked neomycin resistance (neo) cassette downstream of exon 2 of the G protein-coupled receptor 116 (Gpr116) gene. The construct was electroporated into (C57Bl/6J X 129S4/SvJae)F1-derived V6.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to β-actin-Flp transgenic mice to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, and resulting mice were bred to C57BL/6NCrl mice for at least 6 generations. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Adgrf5^tm1.1Bstc
Name: targeted mutation 1.1, Brad St Croix
MGI accession ID: MGI:5490501
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Adgrf5
Marker name: adhesion G protein-coupled receptor F5
Chromosome: 17
Strain of origin: (C57BL/6J x 129S4/SvJae)F1
Molecular note: A targeting vector was designed to insert a loxP site upstream of exon 2 and a frt- and loxP-flanked neomycin resistance (neo) cassette downstream of exon 2. Flp-mediated recombination removed the neo cassette and left exon 2 floxed.