JAX Mouse Strain Datasheet - 013175

B6(Cg)-Grn^tm1.1Aidi/J

Stock No:: 013175 |; PGRN KO

Repository Live

Overview

Also Known As: PGRN KO

In these Grn knock-out mice exons 1-4 are deleted from the targeted granulin (Grn) allele. These mice may be useful for studying inflammatory and infectious diseases, frontotemporal dementia and other neurodegenerative diseases.

Donating Investigator

Aihao Ding, Weill Medical School of Cornell Universi

Genetic overview

Genetic Background	Generation
	N6+N1F2 (06-FEB-17)

Grn^tm1.1Aidi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Grn	granulin

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Research Applications

Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
Neurobiology Research
Research Tools

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Base Price

Starting at:

$255.00 Domestic price for female

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Details

Detailed Description

In these Grn^-/- mice exons 1-4 are deleted from the targeted granulin (Grn) allele. Homozygotes are viable, fertile, and normal in size. These mice show progressive development of frontotemporal dementia-like behavior and neuropathology. This includes enhanced activation of microglia and astrocytes, and ubiquitination and cytoplasmic accumulation of phosphorylated transactivation response element DNA binding protein-43 (TDP-43) in hippocampal and thalamic neurons. By eighteen months they demonstrate impaired spatial learning and memory. Macrophages from these mice release less interleukin-10 and more inflammatory cytokines in response to microbial agents. Contrary to increased inflammation, these mice exhibit a delay in clearing infections due to a dysregulated inflammatory response, allowing bacteria to proliferate in vivo. Activated PGRN-deficient macrophages and microglia are cytotoxic to hippocampal cells, and PGRN-deficient hippocampal slices are hypersusceptible to deprivation of oxygen and glucose. These mice may be useful for studying inflammatory and infectious diseases, frontotemporal dementia and other neurodegenerative diseases.

Development

A targeting vector was designed to insert a single loxP site upstream of the promoter region of the granulin (Grn) gene. A second loxP site 3' to a FRT-flanked neomycin/kanamycin (neo/kan) resistance cassette was placed downstream of exon 4 . The construct was electroporated into C57BL/6-derived C2J embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric mice were bred with mice expressing Cre-recombinase driven by chicken actin gene promoter (CAG-cre; predominately on a C57BL/6 background) to remove the neo/kan selection cassette. Mice lacking both the intact Grn gene and the CAG-cre transgene were backcrossed to C57BL/6 for at least five generations to establish a colony of (Grn^-/-). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Yin F; Banerjee R; Thomas B; Zhou P; Qian L; Jia T; Ma X; Ma Y; Iadecola C; Beal MF; Nathan C; Ding A. 2010. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med 207(1):117-28, S1-4. PubMed: 20026663 MGI: J:156824

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Genetics

Grn^tm1.1Aidi

Allele Symbol: Grn^tm1.1Aidi

Allele Name	targeted mutation 1.1, Aihao Ding
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Grn, granulin
Gene Synonym(s)	CLN11; GEP; GP88; PC cell-derived growth factor; PCDGF; PEPI; PGRN; Pgrn; acrogranulin; epithelin; progranulin
Strain of Origin	B6(Cg)-Tyr
Chromosome	11
General Note	ES cell line = C2J
Molecular Note	Cre mediated recombination removed exons 1 through 4. The absence of protein expression was confirmed by western blot analysis on bone marrow-derived macrophages.
Mutations Made By	Aihao Ding, Weill Medical School of Cornell Universi

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Developmental Biology Research
- Neurodevelopmental Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Macrophage defects
Neurobiology Research
- Behavioral and Learning Defects
- Neurodegeneration
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Macrophage Deficiency
  - genes regulating susceptibility to infectious disease and endotoxin

Mammalian Phenotype Terms by Genotype

Genotype: Grn^tm1.1Aidi/Grn^tm1.1Aidi
involves: C57BL/6 * C57BL/6J

immune system phenotype

abnormal chemokine secretion
- bone marrow-derived macrophages stimulated with Toll-like receptor agonist produce more MCP-1 and CXCL1 compared with similarly treated wild-type cells

abnormal macrophage physiology
- activated bone marrow-derived macrophages exhibit increased killing potential compared with wild-type cells
- bone marrow-derived macrophages stimulated with Toll-like receptor agonist produce more MCP-1, CXCL1, IL6, IL12p40, and TNF compared with similarly treated wild-type cells

abnormal microglial cell physiology
- GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice

increased interleukin-12 secretion
- IL12p40 production is increased in bone marrow-derived macrophages stimulated with Toll-like receptor agonist compared to in similarly treated wild-type cells

increased interleukin-6 secretion
- in bone marrow-derived macrophages stimulated with Toll-like receptor agonist

increased susceptibility to bacterial infection
- following infection with Listeria monocytogenes, mice exhibit fewer monocytes in the spleen and higher Listeria burden in the spleen, liver, and brain compared to in wild-type mice

increased tumor necrosis factor secretion
- in bone marrow-derived macrophages stimulated with Toll-like receptor agonist

microgliosis
- mice exhibit increased age-dependent microgliosis compared with wild-type mice

nervous system phenotype

abnormal microglial cell physiology
- GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice

astrocytosis
- mice exhibit increased age-dependent astrocytosis compared with wild-type mice

microgliosis
- mice exhibit increased age-dependent microgliosis compared with wild-type mice

homeostasis/metabolism phenotype

increased susceptibility to injury
- hippocampal slices starved of glucose and oxygen exhibit increased cell death compared with similarly treated wild-type slices

hematopoietic system phenotype

abnormal macrophage physiology
- activated bone marrow-derived macrophages exhibit increased killing potential compared with wild-type cells
- bone marrow-derived macrophages stimulated with Toll-like receptor agonist produce more MCP-1, CXCL1, IL6, IL12p40, and TNF compared with similarly treated wild-type cells

abnormal microglial cell physiology
- GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice

microgliosis
- mice exhibit increased age-dependent microgliosis compared with wild-type mice

References

Yin F; Banerjee R; Thomas B; Zhou P; Qian L; Jia T; Ma X; Ma Y; Iadecola C; Beal MF; Nathan C; Ding A. 2010. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med 207(1):117-28, S1-4. PubMed: 20026663 MGI: J:156824

Additional - Grn^tm1.1Aidi related

Albuquerque B; Haussler A; Vannoni E; Wolfer DP; Tegeder I. 2013. Learning and memory with neuropathic pain: impact of old age and progranulin deficiency. Front Behav Neurosci 7:174. PubMed: 24319417 MGI: J:241817
Chen X; Chang J; Deng Q; Xu J; Nguyen TA; Martens LH; Cenik B; Taylor G; Hudson KF; Chung J; Yu K; Yu P; Herz J; Farese RV Jr; Kukar T; Tansey MG. 2013. Progranulin does not bind tumor necrosis factor (TNF) receptors and is not a direct regulator of TNF-dependent signaling or bioactivity in immune or neuronal cells. J Neurosci 33(21):9202-13. PubMed: 23699531 MGI: J:198670
Menzel L; Kleber L; Friedrich C; Hummel R; Dangel L; Winter J; Schmitz K; Tegeder I; Schafer MK. 2017. Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury. Glia 65(2):278-292. PubMed: 27778404 MGI: J:237939
Tang W; Lu Y; Tian QY; Zhang Y; Guo FJ; Liu GY; Syed NM; Lai Y; Lin EA; Kong L; Su J; Yin F; Ding AH; Zanin-Zhorov A; Dustin ML; Tao J; Craft J; Yin Z; Feng JQ; Abramson SB; Yu XP; Liu CJ. 2011. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332(6028):478-84. PubMed: 21393509 MGI: J:171041
Wei F; Zhang Y; Zhao W; Yu X; Liu CJ. 2014. Progranulin facilitates conversion and function of regulatory T cells under inflammatory conditions. PLoS One 9(11):e112110. PubMed: 25393765 MGI: J:225148
Zhou X; Sun L; Bastos de Oliveira F; Qi X; Brown WJ; Smolka MB; Sun Y; Hu F. 2015. Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin. J Cell Biol 210(6):991-1002. PubMed: 26370502 MGI: J:227553

Pricing & Availability

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Grn<tm1.1Aidi>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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Licensing Information

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Also Known As: PGRN KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Grntm1.1Aidi

Allele Symbol: Grntm1.1Aidi

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Grntm1.1Aidi/Grntm1.1Aidiinvolves: C57BL/6 * C57BL/6J

immune system phenotype

nervous system phenotype

homeostasis/metabolism phenotype

hematopoietic system phenotype

References

Additional - Grntm1.1Aidi related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Grn^tm1.1Aidi

Allele Symbol: Grn^tm1.1Aidi

Genotype: Grn^tm1.1Aidi/Grn^tm1.1Aidi
involves: C57BL/6 * C57BL/6J

Additional - Grn^tm1.1Aidi related