This targeted mutation deletes exon 2-13 of the mouse progranulin (Grn) gene, abolishing gene function. These mice may be useful in studying the role of progranulin in modulating the kinetics of programmed cell death. 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
Progranulin or granulin precursor (Grn) is 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. This targeted mutation deletes exon 2-13 of the mouse progranulin gene, abolishing gene function. Homozygous mice are viable and fertile. Macrophages cultured from Grn-/- mice exhibit increased levels of phagocytosis of apoptopic thymocytes. These mice may be useful in studying the role of progranulin in modulating the kinetics of programmed cell death.
F2 (B6;129S4) male mice heterozygous for the conditional mutation Grntm1Far mice were crossed to FVB/N-Tg(ACTB-cre)2Mrt females to delete progranulin in the germline. Subsequent matings selected against Tg(ACTB-cre)2Mrt and backcrossed the null allele, Grntm1.1Far, to the inbred strain C57BL/6 for at 7 generations. Mice then were bred to homozygosity. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1.1, Bob Farese|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Grntm1.1Cke; Prgn-|
|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. Cre mediated recombination removed exons 2 to 13. Western blot analysis confirmed the absence of protein expression in peritoneal macrophages from homozygous mice.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the B6.129S4(FVB)-Grntm1.1Far/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36771 in your Materials and Methods section.