|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).|
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Robert V Farese, Jr., Gladstone Institute UCSF
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.
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.
|Considerations for Choosing Controls|
View Strains carrying other alleles of Grn (2 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Grntm1Far/Grntm1Farinvolves: 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 ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Developmental Biology Research
Immunology, Inflammation and Autoimmunity Research
|Allele Name||targeted mutation 1, Bob Farese|
|Allele Type||Targeted (Floxed/Frt)|
|Common Name(s)||Grntm1Cke; PrgnloxP;|
|Strain of Origin||129S4/SvJae|
|Gene Symbol and Name||Grn, granulin|
|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]|
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]
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]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry While maintaining a live colony, these mice are bred as homozygotes.
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