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-East
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|
|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.
When using the IP-10- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006087 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.