B6.129S1-C1galt1^tm1.1Rpmc/LxJ

Stock number: 023713
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These T-syn^F mice may be useful for studying angiogenesis, thrombopoiesis, and kidney homeostasis, as well as some autoimmune diseases.

Detailed description

These T-syn^F mice contain loxP sites flanking exons 1-2 of the core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1 (C1galt1) gene. T-syn facilitates the transfer of galactose (Gal) from Uridine diphosphate (UDP)-Gal to GalNAcα1-Ser/Thr (Tn antigen) to form the core 1 O-glycan, Galβ1-3GalNAcα1-Ser/Thr (T antigen). Tn antigen has been associated with the development of carcinomas and some autoimmune diseases. T-syn plays a role in processes such as angiogenesis, thrombopoiesis, and kidney homeostasis development. O-glycans, are also primary components of mouse colon mucus and plays a protective role against carcinomas and some autoimmune diseases such as ulcerative colitis (UC) and Inflammatory bowel disease (IBD). Homozygotes are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 1-2 deleted in cre-expressing tissues.

For example, when crossed to B6.SJL-Tg(Vil-cre)997Gum/J mice (Stock No. 004586) expressing Cre recombinase in intestinal epithelial cells and crypt cells, double mutant mice, lacking C1galt1 gene expression, develop spontaneous colitis in the distal colon, which is similar to human ulcerative colitis (UC).

Development

A targeting vector was designed to insert a single loxP site upstream of exon 1, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 2 of the core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1 (C1galt1) gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid. Resulting ES cells contained multiple gene rearrangments; intact floxed-exons 1-2, intact floxed-neo cassette, or excision of exons 1-2 and the neo cassette. Correctly targeted ES cells, lacking the floxed-neo cassette, were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females. Resulting T-syn^F mice were bred to C57BL/6J mice for at least 13 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: C1galt1^tm1.1Rpmc
Name: targeted mutation 1.1, Rodger P McEver
MGI accession ID: MGI:3713768
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: C1galt1
Marker name: core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1
Chromosome: 6
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: ES cells containing a loxP site 5' of exon 1 and a floxed neo in intron 2 were transfected with cre recombinase, resulting in the deletion of the neo.
General note: Phenotypic Similarity to Human Syndrome: Premature Ovarian Failure J:125880, J:237228.