Strain Name:

B6(Cg)-Grntm1.1Aidi/J

Stock Number:

013175

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
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.

Description

Strain Information

Former Names B6.Cg-Grntm1.1Aidi/J    (Changed: 23-AUG-10 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   08-NOV-11
Specieslaboratory mouse
GenerationN6+F5 (03-MAY-13)
Generation Definitions
 
Donating Investigator Aihao Ding,   Weill Medical School of Cornell Universi

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 Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Grn
021211   B6.129S4(FVB)-Grntm1.1Far/Mmjax
021210   B6.129S4-Grntm1Far/Mmjax
013174   C57BL/6-Grntm1Aidi/J
View Strains carrying other alleles of Grn     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Ceroid Lipofuscinosis, Neuronal, 11; CLN11   (GRN)
Frontotemporal Lobar Degeneration with Tdp43 Inclusions, Grn-Related   (GRN)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Grntm1.1Aidi/Grntm1.1Aidi

        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   (MGI Ref ID J:156824)
  • abnormal macrophage physiology
    • 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   (MGI Ref ID J:156824)
    • activated bone marrow-derived macrophages exhibit increased killing potential compared with wild-type cells   (MGI Ref ID J:156824)
    • abnormal microglial cell physiology
      • GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice   (MGI Ref ID J:156824)
  • 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   (MGI Ref ID J:156824)
  • increased interleukin-6 secretion
    • in bone marrow-derived macrophages stimulated with Toll-like receptor agonist   (MGI Ref ID J:156824)
  • 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   (MGI Ref ID J:156824)
  • increased tumor necrosis factor secretion
    • in bone marrow-derived macrophages stimulated with Toll-like receptor agonist   (MGI Ref ID J:156824)
  • microgliosis
    • mice exhibit increased age-dependent microgliosis compared with wild-type mice   (MGI Ref ID J:156824)
  • 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   (MGI Ref ID J:156824)
  • astrocytosis
    • mice exhibit increased age-dependent astrocytosis compared with wild-type mice   (MGI Ref ID J:156824)
  • microgliosis
    • mice exhibit increased age-dependent microgliosis compared with wild-type mice   (MGI Ref ID J:156824)
  • 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   (MGI Ref ID J:156824)
  • hematopoietic system phenotype
  • abnormal macrophage physiology
    • 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   (MGI Ref ID J:156824)
    • activated bone marrow-derived macrophages exhibit increased killing potential compared with wild-type cells   (MGI Ref ID J:156824)
    • abnormal microglial cell physiology
      • GM-CSF and LPS/IFN-gamma treated mice exhibit increased cytotoxicity compared with similarly treated wild-type mice   (MGI Ref ID J:156824)
  • microgliosis
    • mice exhibit increased age-dependent microgliosis compared with wild-type mice   (MGI Ref ID J:156824)
View Research Applications

Research Applications
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

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Grntm1.1Aidi
Allele Name targeted mutation 1.1, Aihao Ding
Allele Type Targeted (knock-out)
Mutation Made By Aihao Ding,   Weill Medical School of Cornell Universi
Strain of OriginB6(Cg)-Tyr
Gene Symbol and Name Grn, granulin
Chromosome 11
Gene Common Name(s) CLN11; GEP; GP88; PC cell-derived growth factor; PCDGF; PEPI; PGRN; acrogranulin; epithelin; progranulin;
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. [MGI Ref ID J:156824]

Genotyping

Genotyping Information

Genotyping Protocols

Grntm1.1Aidi, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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 Ref ID J:156824]

Additional References

Grntm1.1Aidi related

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 Ref ID J:198670]

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 Ref ID J:171041]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a colony, homozygotes may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   08-NOV-11
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $195.00Female or MaleHomozygous for Grntm1.1Aidi  
Price per Pair (US dollars $)Pair Genotype
$390.00Homozygous for Grntm1.1Aidi x Homozygous for Grntm1.1Aidi  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $253.50Female or MaleHomozygous for Grntm1.1Aidi  
Price per Pair (US dollars $)Pair Genotype
$507.00Homozygous for Grntm1.1Aidi x Homozygous for Grntm1.1Aidi  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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