B6.Cg-Sntb1^tm1.1Scf/J

Stock number: 035532
Product name: Sntb1^flox
Research areas: Neurobiology Research, Research Tools

Description

Sntb1^flox mice have loxP sites flanking exon 1 of the Sntb1 gene. These mice may be useful when studying the dystrophin complex and Duchenne muscular dystrophy.

Detailed description

Sntb1^flox mice have loxP sites flanking exon 1 of the syntrophin, basic 1 (Sntb1) gene. Syntrophins are a family of 58-60 kDa proteins consisting of five isoforms (α, β1, β2, γ1 and γ2) encoded by separate genes. α, β1, and β2 have multiple binding motifs and directly bind to dystrophin, utrophin and dystrobrevin, where they recruit and anchor a variety of signaling proteins. Specifically, β1-Syntrophin encodes a dystrophin associated protein expressed on the sarcolemma of skeletal muscle fast fibers. Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in Duchenne Muscular Dystrophy (DMD) patients and is present in reduced amounts in Becker Muscular Dystrophy patients. Muscular Dystrophy is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of dystrophin that helps keep muscle cells intact. Mice that are homozygous for this β1-Syntrophin floxed allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 of Sntb1 deleted in the cre-expressing tissues.

When Sntb1^flox mice are bred to CMV-cre mice, with widespread Cre expression, resulting β1KO mice are viable and fertile with no overt phenotype and show no discernable muscle myopathy by histochemical techniques. α-syntrophin is upregulated in liver and skeletal muscle from these KO mice, showing a compensatory role between isoforms.

β1KO mice are also bred to αKO mice (Stock No. 012940) and β2KO mice (Stock No. 035533) to produce triple syntrophin knockout (tKO) mice. tKO mice exhibit diminished function and reduced dystrophin expression in both cardiac and skeletal muscle.

Development

The Sntb1^flox targeting vector was designed to insert a loxP site upstream of exon 1 of the syntrophin, basic 1 (Sntb1) gene, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of exon 1. The construct was electroporated into (C3H x C57BL/6)F1-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into (C3H x C57BL/6)F1 recipient blastocysts. The resulting Sntb1^flox chimeric mice were bred to FLP mice on a C57BL/6 background to remove the neo cassette and offspring were crossed to remove the flp expressing transgene. Resulting mice were backcrossed to C57BL/6J mice (Stock No. 000664) for at least 10 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

In 2021, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Three of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Sntb1^tm1.1Scf
Name: targeted mutation 1.1, Stanley C Froehner
MGI accession ID: MGI:6304308
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Sntb1^tm1.1Maad
Marker symbol: Sntb1
Marker name: syntrophin, basic 1
Marker synonyms: 59-1 DAP; 59-DAP; A1B; beta1-Syntrophin; BSYN2; DAPA1B; SNT2; SNT2B1; TIP-43
Chromosome: 15
Strain of origin: (C3H x C57BL/6)F1
Molecular note: A loxP site was inserted upstream of exon 1 and an FRT site flanked neomycin resistance gene cassette and a second loxP site into intron 1. Subsequent flp-mediated recombination removed the neo cassette, leaving a conditional-ready allele with exon 1 floxed.