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).
Robert V Farese, Jr., Harvard University School of Public Health
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.
|Allele Name||targeted mutation 1, Bob Farese|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Grntm1Cke; PrgnloxP|
|Gene Symbol and Name||Grn, granulin|
|Strain of Origin||129S4/SvJae|
|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.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the B6.129S4-Grntm1Far/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36770 in your Materials and Methods section.