Homozygous mice have defective T cell responses, including impaired proliferation and IFN-gamma secretion following antigenic challenge. Contact hypersensitivity is reduced and ability to control viral replication in the brain after infection is impaired. These mutant mice may be useful in studies of Th1-type inflammatory disease, chemokine biology, and T cell priming, proliferation, and trafficking.
Andrew D Luster, Massachusetts General Hospital-EastRead More +
Homozygous mice are viable, fertile, and have no overt morphological or developmental abnormalities. No endogenous gene expression is observed in bone marrow-derived macrophages before or after IFN-gamma stimulation. Homozygous mice have defective T cell responses, including impaired proliferation and IFN-gamma secretion following antigenic challenge (129Sv background). In experimental models of T helper-1 (Th1)-mediated immune responses, homozygous-deletion leads to diminished immune function; contact hypersensitivity is reduced (129Sv background) and diminished threshold for disease expression in experimental autoimmune encephalomyelitis (EAE, human model of multiple sclerosis) (C57BL/6 background). After injection with a neurotropic coronavirus MHV, null mice (on a B6;129Sv background) exhibit impaired viral clearance, decreased CD4+/CD8+ infiltration into the brain, and are protected from viral-induced demyelination. Similarly, homozygous mice (on a C57BL/6 background) infected with West Nile Virus have increased viral load in brain, altered CD8+ effector T cell recruitment to neurons and increased mortality. These mutant mice may be useful in studies of Th1-type inflammatory disease, chemokine biology, and T cell priming, proliferation, and trafficking.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for this strain. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing a mouse phosphoglycerate kinase promoter driven neomycin resistance gene was used to replace exons 1-3 of the endogenous gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric mice were bred to C57BL/6 to generate mice heterozygous for the mutant allele. Mutant mice were mated to C57BL/6 mice for nine generations and then made homozygous before arriving at The Jackson Laboratory Repository in 2006 (see SNP results below). Upon arrival, homozygous animals were bred together to generate our living colony. Some homozygous males were used to cryopreserve sperm in 2006. In October 2012, the living colony was bred one generation to C57BL/6J inbred mice, and thereafter maintained by breeding homozygous mice together.
In 2013, a 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating in one breeding pair derived from a single outcross with C57BL/6J animals. All other breeding pairs descended from breeding homozygous mice together (no outcrossing to C57BL/6J) were found to be homozygous for the C57BL/6N markers. These data suggest that the living colony (and sperm cryopreserved in 2006) was on a C57BL/6N genetic background up to October 2012. The living colony now is a mix of C57BL/6N and C57BL/6J.
|Allele Name||targeted mutation 1, Andrew D Luster|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cxcl10, chemokine (C-X-C motif) ligand 10|
|Gene Synonym(s)||C7; CRG-2; IFI10; INP10; IP-10; IP10; Ifi10; Ifi10; SCYB10; Scyb10; Scyb10; crg-2; gIP-10; interferon activated gene 10; mob-1; small inducible cytokine B subfamily (Cys-X-Cys), member 10|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Exons 1-3, which encompass most of the coding region of the gene, were replaced with a PGK-neo cassette via homologous recombination. Northern and Western blot analyses of bone marrow macrophages confirmed the absence of gene expression in homozygous mutant animals.|
|Mutations Made By|| |
Andrew Luster, Massachusetts General Hospital-East
When maintaining a live colony, these mice are bred as homozygotes.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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