These Grn floxed mutant mice possess a single loxP site upstream of the promoter region of the granulin (Grn) gene, and a second loxP site fused to a FRT-flanked neomycin/kanamycin (neo/kan) resistance cassette downstream of exon 4. This floxed strain may be used to generate whole mouse or tissue-specific mutants that are useful for studying inflammation, infectious disease, frontotemporal dementia and other neurodegenerative diseases.
Aihao Ding, Weill Medical School of Cornell Universi
These Grn floxed mutant mice possess a single loxP site upstream of the promoter region of the granulin (Grn) gene, and a second loxP site fused to a FRT-flanked neomycin/kanamycin (neo/kan) resistance cassette downstream of exon 4. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 1- 4 deleted in cre-expressing tissues. When bred with mice expressing Cre-recombinase driven by the chicken actin gene promoter (CAG-cre), granulin deficiency is widespread (see Stock No. 013175). These mice exhibit neurodegeneration as seen in human frontotemporal dementia and have an exaggerated inflammation response when exposed to microbial agents. This floxed strain may be used to generate whole mouse or tissue-specific mutants that are useful for studying inflammation, infectious disease, frontotemporal dementia and other neurodegenerative diseases.
A targeting vector was designed to insert a single loxP site upstream of the promoter region, and a second loxP site 3' of a FRT-flanked neomycin/kanamycin (neo/kan) resistance cassette were placed downstream of exon 4 of the granulin (Grn) gene. The construct was electroporated into c2J embryonic stem (ES) cells (derived from albino C57BL/6J-Tyrc-2j mice). Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with albino C57BL/6J-Tyrc-2j mice. Resulting offspring were bred together to establish a colony of Grnflox/flox mice. Upon arrival at The Jackson Laboratory, Grnflox/flox mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. These mutant mice may still be segregating for the Tyrc-2J mutation.
|Allele Name||targeted mutation 1, Aihao Ding|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|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 |
|General Note||ES cell line = C2J|
|Molecular Note||A loxP site was inserted upstream of exon 1 and an frt floxed neo cassette with a 3' loxP site was inserted downstream of exon 4.|
|Mutations Made By|| |
Aihao Ding, Weill Medical School of Cornell Universi
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