B6.129P2-Pzp^tm1Vln Mug1^tm2Vln/J

Stock number: 024839

Description

This strain is Under Development for CRYO and will be removed from the shelf in the near future. Please register interest if you would like to obtain mice from the live colony.

This strain is reported to carry a mutation in the A2m, alpha-2-macroglubulin gene (Umans et al.,1995). Genomic analysis suggests the mutation occurs in a closely related gene, Pzp (pregnancy zone protein). Conversely, the use of an anti-murine A2m Elisa kit by some suggests loss of the serological A2m protein. We will update this datasheet as clarifying studies are published. (8/2017)

These double knock-out mice exhibit increased mortality to experimentally induced pancreatitis. They are suitable for use in applications related to the study of inflammatory disease.

Detailed description

This strain is reported to carry a mutation in the A2m, alpha-2-macroglubulin gene (Umans et al.,1995). Genomic analysis suggests the mutation occurs in a closely related gene, Pzp (pregnancy zone protein). Conversely, the use of an anti-murine A2m Elisa kit by some suggests loss of the serological A2m protein. We will update this datasheet as clarifying studies are published. (8/2017)

These mice carry knock out alleles for the Mug1 and Pzp genes. Mice that are homozygous for the targeted mutation are viable and fertile, but smaller in size than wildtype controls. No gene product (mRNA) for either gene is detected by Northern blot analysis of liver. Double mutant mice on the C57BL/6 background exhibit higher susceptibility and mortality to experimentally induced acute hemorrhagic pancreatitis (using the Choline- and methionine-deficient powder diet, CDE) than mice on the mixed B6;129 background. Double homozygous matings yield slight smaller litters (approximately 5 pups/litter) compared to wildtype controls (approximately 7 pups/litter). Double mutant mice fed the CDE diet develop hepatic cell necrosis, vacuolation and inflammatory infiltration of the liver. Pregnant females in double homozygous matings exhibit abnormalities in maternal decidua, uterine spiral artery, and fewer uterine NK cells. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Development

A targeting vector containing a PGK-NEO selection cassette was used to disrupt exon 18 and part of exon 19 of the Mug1, murinoglobulin 1, gene. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells that contained a targeted mutation of PGK-hygromycin selection cassette disrupting the Pzp, pregnancy zone protein gene. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6 for more than 10 generations (see SNP note below). During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background. Double heterozygotes were crossed to produce double homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 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/6J ; C57BL/6N genetic background.

Allele

Symbol: Mug1^tm2Vln
Name: targeted mutation 2, Fred Van Leuven
MGI accession ID: MGI:3700943
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Mug1
Marker name: murinoglobulin 1
Chromosome: 6
Strain of origin: 129P2/OlaHsd
Molecular note: A targeting construct containing a neomycin resistance gene was inserted into ES cells containing a previously targeted insertion of a hygromycin cassette into exon 17 of the Pzp locus. Deficiency of both proteins was confirmed by Northern blot of mutant liver samples.

Allele

Symbol: Pzp^tm1Vln
Name: targeted mutation 1, Fred Van Leuven
MGI accession ID: MGI:2180117
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Pzp
Marker name: PZP, alpha-2-macroglobulin like
Chromosome: 6
Strain of origin: 129P2/OlaHsd
Molecular note: A construct was created by replacing 0.7-kb of intron 17 with PKC-hygro. Northern analysis of RNA isolated from the livers of homozygous mice showed an absence of transcript. Rocket immunoelectrophoresis also showed no expression.