B6(DBA)-Nphs1^tm1Afrn/J

Stock number: 027824
Product name: NP floxed
Research areas: Cell Biology Research, Developmental Biology Research, Diabetes and Obesity Research, Endocrine Deficiency Research, Internal/Organ Research, Research Tools

Description

NP^flox mice possess loxP sites flanking exon 1B-5 of the nephrosis 1, nephrin (Nphs1) gene. They may be useful for studying glucose-stimulated insulin response, as well as islet and podocyte survival.

Detailed description

NP^flox mice possess loxP sites flanking exon 1B-5 of the nephrosis 1, nephrin (Nphs1) gene. A frt-flanked neo cassette is still present in these mice and it is unknown if it is expressed. Mice that are heterozygous for this allele are viable and fertile. The donating investigator has not attempted to breed homozygotes. Nephrin is a member of a family of cell adhesion modulating proteins. Nephrin in the kidneys regulates glomerular vascular permeability. Also expressed in pancreatic islets, nephrin plays a role in beta cell function and survival. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 1B-5 deleted in cre-expressing tissues.

For example, when crossed to B6.Cg-Tg(Ins2-Cre)25Mgn/J mice (Stock No. 003573) expressing Cre recombinase in pancreatic beta cells, NP deficient mice exhibit glucose intolerance and reduced glucose-stimulated insulin response, with no effect on islet size or glycemia.

Development

A targeting vector was designed to insert one loxP site upstream of exon 1B, one loxP site upstream of exon 1A, and a frt-flanked polyA site and a neomycin resistance (neo) cassette, followed by a third loxP site, downstream of exon 5 of the nephrosis 1, nephrin (Nphs1) gene. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with C57BL/6J mice. Heterozygous NP^flox mice were bred to B6.Cg-Tg(Ins2-Cre)25Mgn/J mice (Stock No. 003573) mice and resulting mice WT for Cre were subsequently backcrossed for 10 generations to C57BL/6J. Upon arrival at The Jackson Laboratory, these mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish a colony.

Allele

Symbol: Nphs1^tm1Afrn
Name: targeted mutation 1, Alessia Fornoni
MGI accession ID: MGI:5661391
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Nphs1
Marker name: nephrosis 1, nephrin
Chromosome: 7
Strain of origin: C57BL/6
Molecular note: The targeting vector is designed to insert one loxP site upstream of exon 1B, one loxP site upstream of exon 1A, and an FRT-flanked polyA site and a neomycin resistance (neo) cassette followed by a third loxP site downstream of exon 5.