Strain Name:

B6.129S4-Grntm1Far/Mmjax

Availability:

Cryopreserved - Ready for recovery     Available at the JAX MMRRC

Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6.129S4-Grntm1Far/Mmjax MMRRC Stock Number 036770.
These Grnflox mutant mice possess loxP sites flanking the whole coding sequence of the granulin precursor (or progranulin) gene. Progranulin is associated with wound healing, inflammation, embryogenesis, tumor growth and the human neurodegenerative syndrome, frontotemporal lobar dementia (FTLD).

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Robert V Farese, Jr.,   Gladstone Institute UCSF

Description
These Grnflox mutant mice possess loxP sites flanking exons 2-13, which comprises the coding sequence and the 3'UTR of the granulin precursor (or progranulin) gene. Progranulin is a glycopeptide secreted by many cell types and is processed into growth modulating peptides called granulins. The human neurodegenerative syndrome frontotemporal lobar dementia (FTLD) is associated with mutations in progranulin. Progranulin also is associated with wound healing, inflammation, embryogenesis and tumor growth. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have a null allele in the cre-expressing tissues.

For example, when bred to mice carrying Tg(ACTB-cre)2Mrt,widespread Cre recombinase expression results in macrophages that exhibit increased levels of phagocystosis in culture and when treated with MPTP Grn- mice exhibit an increased loss of dopaminergic neurons and increased numbers of activated microglia.

Development
A targeting vector was designed to insert loxP sites flanking exons 2 to 13 (the entire coding sequence and the 3' UTR) and a neomycin cassette downstream of the polyA signal. The construct was electroporated into 129S4/SvJae-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice for at least 9 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Grn
013175   B6(Cg)-Grntm1.1Aidi/J
021211   B6.129S4(FVB)-Grntm1.1Far/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

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

Grntm1Far/Grntm1Far

        involves: 129S4/SvJae * C57BL/6J * FVB/N   (conditional)
  • nervous system phenotype
  • abnormal neuron physiology
    • following treated with LPS and IFN-gamma, primary cultures from mice infected a lentivirus expressing cre in microglia exhibit increased neuron death compared with controls   (MGI Ref ID J:188324)
View Research Applications

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

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cancer Research
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Grntm1Far
Allele Name targeted mutation 1, Bob Farese
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Grntm1Cke; PrgnloxP;
Strain of Origin129S4/SvJae
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;
Molecular Note LoxP sites were inserted flanking exons 2 to 13 and a neo cassette was inserted downstream of the polyadenylation signal via homologous recombination. [MGI Ref ID J:170823]

Genotyping

Genotyping Information

Genotyping Protocols

Grntm1Faralternate1, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kao AW; Eisenhut RJ; Martens LH; Nakamura A; Huang A; Bagley JA; Zhou P; de Luis A; Neukomm LJ; Cabello J; Farese RV Jr; Kenyon C. 2011. A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells. Proc Natl Acad Sci U S A 108(11):4441-6. [PubMed: 21368173]  [MGI Ref ID J:170823]

Additional References

Grntm1Far related

Filiano AJ; Martens LH; Young AH; Warmus BA; Zhou P; Diaz-Ramirez G; Jiao J; Zhang Z; Huang EJ; Gao FB; Farese RV Jr; Roberson ED. 2013. Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice. J Neurosci 33(12):5352-61. [PubMed: 23516300]  [MGI Ref ID J:196590]

Martens LH; Zhang J; Barmada SJ; Zhou P; Kamiya S; Sun B; Min SW; Gan L; Finkbeiner S; Huang EJ; Farese RV Jr. 2012. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J Clin Invest :. [PubMed: 23041626]  [MGI Ref ID J:188324]

Rosen EY; Wexler EM; Versano R; Coppola G; Gao F; Winden KD; Oldham MC; Martens LH; Zhou P; Farese RV Jr; Geschwind DH. 2011. Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling. Neuron 71(6):1030-42. [PubMed: 21943601]  [MGI Ref ID J:178551]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Supply Notes


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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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