Overview

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.

Donating Investigator

Fred Van Leuven, Experimental Genetics Group - KULeuven

Genetic overview

Genetic Background	Generation

Pzp^tm1Vln

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Pzp	PZP, alpha-2-macroglobulin like

Mug1^tm2Vln

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Mug1	murinoglobulin 1

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Umans L; Serneels L; Overbergh L; Stas L; Van Leuven F. 1999. alpha2-macroglobulin- and murinoglobulin-1- deficient mice. A mouse model for acute pancreatitis. Am J Pathol 155(3):983-93PubMed: 10487856 MGI: J:57485

View All References

Genetics

Pzp^tm1Vln

Allele Symbol: Pzp^tm1Vln

Allele Name	targeted mutation 1, Fred Van Leuven
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	MAM^-
Gene Symbol and Name	Pzp, PZP, alpha-2-macroglobulin like
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	6
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.
Mutations Made By	Fred Van Leuven, Experimental Genetics Group - KULeuven

Mug1^tm2Vln

Allele Symbol: Mug1^tm2Vln

Allele Name	targeted mutation 2, Fred Van Leuven
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	MAM^-/MUG-1^-
Gene Symbol and Name	Mug1, murinoglobulin 1
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	6
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.
Mutations Made By	Fred Van Leuven, Experimental Genetics Group - KULeuven

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mug1^tm2Vln/Mug1^tm2Vln Pzp^tm1Vln/Pzp^tm1Vln
B.129P2-Pzp Mug1

cardiovascular system phenotype

abnormal placenta vasculature
- intravascular uterine NK cells are observed in placental arteries

endocrine/exocrine gland phenotype

abnormal uterine NK cell morphology
- at gd 10, frequency of uterine natural killer (uNK) cells per unit area of decidua basalis is significantly less than in wild-type
- some cells show early degenerative changes, including nuclear chromatin margination and mitochondrial swelling at gd10 and 11, whereas in wild-type, such changes aren't seen until after gd 12

growth/size/body region phenotype

decreased body weight
- at 4, 6, and 8 weeks, female mean weights are 11.2, 14.9, and 17.5 g compared to 14.3, 18.4, and 19 g for wild-type females; male mean weights 12.7, 18.5, and 22.5 g vs 17.1, 22.8, and 25.2 g for wild-type analyzed at same time points as females
- pups are smaller than wild-type pups

hematopoietic system phenotype

abnormal uterine NK cell morphology
- some cells show early degenerative changes, including nuclear chromatin margination and mitochondrial swelling at gd10 and 11, whereas in wild-type, such changes aren't seen until after gd 12
- at gd 10, frequency of uterine natural killer (uNK) cells per unit area of decidua basalis is significantly less than in wild-type

homeostasis/metabolism phenotype

abnormal cytokine level
- after 3 days of CDE diet, some cytokines are upregulated in pancreas of some affected mice

increased circulating amylase level
- after 66 hours of CDE diet, amylase plasma concentrations are significantly higher than in wild-type

increased circulating lipase level
- after 66 hours of CDE diet, lipase plasma concentrations are significantly higher than in wild-type

cellular phenotype

hepatic necrosis
- observed after 2-3 days of CDE diet, along with large vacuole formation and remains unchanged afterwards

immune system phenotype

abnormal uterine NK cell morphology
- some cells show early degenerative changes, including nuclear chromatin margination and mitochondrial swelling at gd10 and 11, whereas in wild-type, such changes aren't seen until after gd 12
- at gd 10, frequency of uterine natural killer (uNK) cells per unit area of decidua basalis is significantly less than in wild-type

liver inflammation
- inflammatory cell infiltrate is observed after 2-3 days of CDE diet
- liver abnormalities are reversed by 4 days of normal diet

abnormal cytokine level
- after 3 days of CDE diet, some cytokines are upregulated in pancreas of some affected mice

liver/biliary system phenotype

liver inflammation
- inflammatory cell infiltrate is observed after 2-3 days of CDE diet
- liver abnormalities are reversed by 4 days of normal diet

hepatic necrosis
- observed after 2-3 days of CDE diet, along with large vacuole formation and remains unchanged afterwards

mortality/aging

increased sensitivity to induced morbidity/mortality
- l mice
- on a choline and methionine-deficient powder diet supplemented with ethionine (CDE) designed to induce acute hemorrhagic pancreatitis, mortality is 60% after 5 days on the diet compared to only 23% in mutants on a mixed background or 70% in Pzp-single null mice

prenatal lethality, incomplete penetrance
- resorption sites are observed around midgestation indicating reduced viability

reproductive system phenotype

abnormal uterine NK cell morphology
- at gd 10, frequency of uterine natural killer (uNK) cells per unit area of decidua basalis is significantly less than in wild-type
- some cells show early degenerative changes, including nuclear chromatin margination and mitochondrial swelling at gd10 and 11, whereas in wild-type, such changes aren't seen until after gd 12

abnormal uterine environment
- at gd 10, frequency of uterine natural killer cells per unit area of decidua basalis is significantly less than in wild-type

abnormal decidualization
- decidual cells contain smaller nuclei and cells are hypotrophic than wild-type cells at gestational day (gd) 10

abnormal uterine spiral artery morphology
- these perivascular and intramural trophoblast cells extend to the myometrial circular smooth muscle but do not cross it on gd 10-12; this depth of invasion does not occur until ~gd 18 in wild-type
- at gd 10-12, decidual spiral arteries are widely dilated but abnormally cuffed by large trophoblast cells which are embedded in spiral artery walls and surround the entire vessel circumference; this is not observed in wild-type

decreased litter size
- homozygous matings yield slightly smaller litters (4.9 pups/litter) vs control data for wild-type (6.1-7.6 pups/litter)

abnormal maternal decidual layer morphology
- intracellular spaces between decidual cells is increased at gd 10

embryo phenotype

abnormal placenta labyrinth morphology
- cytoplasm of trophoblast cells contain more phagolysosomes and lamellar bodies than wild-type

abnormal maternal decidual layer morphology
- intracellular spaces between decidual cells is increased at gd 10

abnormal placenta vasculature
- intravascular uterine NK cells are observed in placental arteries

abnormal trophoblast layer morphology
- deciduas/trophoblast interface is abnormal with typical dome of trophoblast giant cells extensively disrupted by compact tissue made of large eosinophilic cells extending into decidua basalis almost reaching circular smooth muscle

abnormal uterine NK cell morphology
- at gd 10, frequency of uterine natural killer (uNK) cells per unit area of decidua basalis is significantly less than in wild-type
- some cells show early degenerative changes, including nuclear chromatin margination and mitochondrial swelling at gd10 and 11, whereas in wild-type, such changes aren't seen until after gd 12

abnormal decidualization
- decidual cells contain smaller nuclei and cells are hypotrophic than wild-type cells at gestational day (gd) 10

abnormal uterine spiral artery morphology
- at gd 10-12, decidual spiral arteries are widely dilated but abnormally cuffed by large trophoblast cells which are embedded in spiral artery walls and surround the entire vessel circumference; this is not observed in wild-type
- these perivascular and intramural trophoblast cells extend to the myometrial circular smooth muscle but do not cross it on gd 10-12; this depth of invasion does not occur until ~gd 18 in wild-type

Genotype: Mug1^tm2Vln/Mug1^tm2Vln Pzp^tm1Vln/Pzp^tm1Vln
involves: 129P2/OlaHsd * C57BL

mortality/aging

abnormal induced morbidity/mortality
- Background Sensitivity - on a choline and methionine-deficient powder diet supplemented with ethionine (CDE), designed to induce acute hemorrhagic pancreatitis, mortality is 23% after 5 days on the diet compared to 60% in mutants on a congenic B6 background

References

Umans L; Serneels L; Overbergh L; Stas L; Van Leuven F. 1999. alpha2-macroglobulin- and murinoglobulin-1- deficient mice. A mouse model for acute pancreatitis. Am J Pathol 155(3):983-93PubMed: 10487856 MGI: J:57485

Additional - Mug1^tm2Vln related

Additional - Pzp^tm1Vln related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Mug1-Alternate 3
- Separated PCR:Pzp Alternate 3
- QPCR:Generic Hygromycin
- QPCR:Generic Neo Quantitative PCR-QPCR- 1.2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as double homozygotes. Double homozygous matings yield slight smaller litters (approximately 5 pups/litter) compared to wildtype controls (approximately 7 pups/litter).
- Additional Breeding and Husbandry Support
Mating System
- When maintaining a live colony, these mice can be bred as double homozygotes
Citation
When using the B6.129P2-Pzp^tm1Vln Mug1^tm2Vln/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024839 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for A2m<tm1Vln>, Heterozygous for Mug1<tm2Vln>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Pzp<tm1Vln> Mug1<tm2Vln>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-Pzp<tm1Vln> Mug1<tm2Vln>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-Pzp<tm1Vln> Mug1<tm2Vln>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129P2-Pzp<tm1Vln> Mug1<tm2Vln>/J Frozen Embryo	$3373.50

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Pzptm1Vln

Allele Symbol: Pzptm1Vln

Mug1tm2Vln

Allele Symbol: Mug1tm2Vln

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Mug1tm2Vln/Mug1tm2Vln Pzptm1Vln/Pzptm1VlnB.129P2-Pzp Mug1

cardiovascular system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

reproductive system phenotype

embryo phenotype

Genotype: Mug1tm2Vln/Mug1tm2Vln Pzptm1Vln/Pzptm1Vlninvolves: 129P2/OlaHsd * C57BL

mortality/aging

References

Additional - Mug1tm2Vln related

Additional - Pzptm1Vln related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Pzp^tm1Vln

Allele Symbol: Pzp^tm1Vln

Mug1^tm2Vln

Allele Symbol: Mug1^tm2Vln

Genotype: Mug1^tm2Vln/Mug1^tm2Vln Pzp^tm1Vln/Pzp^tm1Vln
B.129P2-Pzp Mug1

Genotype: Mug1^tm2Vln/Mug1^tm2Vln Pzp^tm1Vln/Pzp^tm1Vln
involves: 129P2/OlaHsd * C57BL

Additional - Mug1^tm2Vln related

Additional - Pzp^tm1Vln related