B6.Cg-Crlf2^tm1.1Sfz/J

Stock number: 040455
Product name: Tslpr^fl
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Tslpr^fl/fl floxed mice have loxP sites flanking exons 3-4 of the Crlf2 gene. These mice may be useful when studying the role of the epithelial-derived cytokine, thymic stromal lymphopoietin (TSLP), in promoting allergic inflammation and tumorigenesis.

This allele is also available on a congenic BALB/c genetic background as Stock No. 040496.

Detailed description

Tslpr^fl/fl floxed mice have loxP sites flanking exons 3-4 of the cytokine receptor-like factor 2 (Crlf2) gene. Crlf2 encodes the receptor for thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine produced primarily by epithelial cells at barrier surfaces, including in the colon. TSLP is an important regulator of Th2-type responses in the skin, lung, and gastrointestinal tract and has been implicated in atopic march, the progression of allergic diseases, typically starting in early childhood. The binding of TSLP to its receptor, TSLPR, results in a signal cascade leading to the upregulation of pro-inflammatory cytokines such as IL-4, IL-5, IL-9, and IL-13. TSLP has also been shown to directly promote the progression and metastasis of several human cancers, including breast, pancreatic, gastric and cervical cancer, and B cell lymphoma and myeloma.

Homozygous Tslpr^fl/fl mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissues.

Of note, this allele is also available on a congenic BALB/c genetic background as Stock No. 040496.

Development

The Tslpr^fl targeting vector was designed to insert a loxP site upstream of exon 3 of the cytokine receptor-like factor 2 (Crlf2) gene, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 4. The construct was electroporated into embryonic stem (ES) cells with an unknown genetic background. Correctly targeted ES cells were injected into blastocysts and the chimeric mice were bred to Flp deleter mice to remove the neo cassette. Resulting Tslpr^fl floxed offspring were bred to C57BL/6J mice for at least 12 generations by the donating laboratory (see SNP note below). Cryopreserved sperm was sent to The Jackson Laboratory. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

In 2025, 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. Four of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the sperm sent to The Jackson Laboratory Repository was on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Crlf2^tm1.1Sfz
Name: targeted mutation 1.1, Steven F Ziegler
MGI accession ID: MGI:5708846
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Tslpr^fl
Marker symbol: Crlf2
Marker name: cytokine receptor-like factor 2
Marker synonyms: Crl2; CRLF2Y; Ly114; Tpte2; TSLPR
Chromosome: 5
Strain of origin: Not Specified
Molecular note: A loxP site was inserted upstream of exon 3 and an FRT flanked neo cassette and loxP site were inserted downstream of exon 4 via homologous recombination. Flp mediated recombination removed the neo cassette.