B6.129S6-Tnfaip8l2^tm1Yhcn/J

Stock number: 039210
Product name: TIPE2-deficient
Strain synonyms: TIPE2^-
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research

Description

TIPE2-deficient mice have a neo cassette the entire coding region included in exons 1 and 2 of the Tnfaip8l2 gene, abolishing endogenous gene expression. These mice may be useful for studying the role of TIPE2 on inflammatory responses during the onset of chronic inflammatory diseases and bacterial infection.

Detailed description

TIPE2-deficient mice have a neo cassette the entire coding region included in exons 1 and 2 of the tumor necrosis factor, alpha-induced protein 8-like 2 (Tnfaip8l2) gene, abolishing endogenous gene expression. TIPE2 is a member of the TNFAIP8 family and is preferentially expressed in hematopoietic cells where it serves as a negative regulator of immunity and helps to maintain immune homeostasis. Abnormal expression of TIPE2 has been associated with several diseases, including autoimmune diseases, bacterial infection, chronic inflammatory diseases, and cancer.

Unlike TIPE2-deficient mice on a 129 genetic background that develop systemic inflammation early in their lives, these TIPE2-deficient mice on a C57BL/6J genetic background are relatively healthy, with a normal gastrointestinal tract.

When colitis is induced by supplementing dextran sodium sulfate (DSS) into their water, the severity of the colitis is reduced in TIPE2-deficient mice compared to wildtype mice. Also, mortality and weight loss is reduced. These mice produce significantly less proinflammatory cytokines, such as TNF-α, IL-6, and IL-12, relative to WT mice, yet they produce comparable amounts of IL-1β, IL-4, and IFN-&gamma to WT mice.

Tumor growth in TIPE2-deficient mice is significantly diminished, and TIPE2-deficient myeloid-derived suppressor cells (MDSCs) directly mediate antitumor responses.

Development

A targeting vector was designed to replace the entire coding region included in exons 1 and 2 of the tumor necrosis factor, alpha-induced protein 8-like 2 (Tnfaip8l2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting TIPE2-deficient chimeric males were crossed with 129S6/SvEvTac females. Subsequently, mice were backcrossed to C57BL/6J mice (Stock No. 000664) for at least 12 generations. 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.

Allele

Symbol: Tnfaip8l2^tm1Yhcn
Name: targeted mutation 1, Youhai H Chen
MGI accession ID: MGI:3810526
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: TIPE2^-
Marker symbol: Tnfaip8l2
Marker name: tumor necrosis factor, alpha-induced protein 8-like 2
Marker synonyms: 1810019A08Rik; RGD1310519; Tipe2; TNFAIP8L2
Chromosome: 3
Strain of origin: 129S6/SvEvTac
Molecular note: Both exons of this gene locus were replaced by a neomycin resistance cassette. RT-PCR on bone marrow confirmed gene inactivation.