Production of macrophage cytokines in response to stimulation with lipopolysaccharide, peptidoglycan and double-stranded RNA is reduced in these Ripk2 KO mice, making them suitable for use in studies of innate and adaptive immune system signaling.
Dr. Richard A. Flavell, Yale University School of Medicine
Rip2 KO mice contain a neo cassette in reverse orientation in place of exons 2-3 of the Ripk2 (receptor (TNFRSF)-interacting serine-threonine kinase 2) gene. Cytokine production in macrophages is reduced in homozygotes upon stimulation with lipopolysaccharide, peptidoglycan and double-stranded RNA, but not with bacterial DNA. RIPK2 deficient cells are also hyporesponsive to signaling through IL1 and IL18 interleukin receptors, and deficient for signaling through NOD (nucleotide-binding oligomerization domain) proteins. T cells show severely reduced NFKB (nuclear factor of kappa light chain gene enhancer in B-cells) activation, IL2 production and proliferation on T cell receptor (TCR) engagement, and impaired differentiation to T-helper subtype 1 (TH1)cells. Western blot analysis of thymocytes demonstrates the absence of protein in homozygous mutant mice. Homozygotes are viable and fertile.
A targeting vector was designed to replace exons 2-3 of the receptor (TNFRSF)-interacting serine-threonine kinase 2 (Ripk2) gene, encoding the active site aspartate residue, with a loxP-flanked neomycin resistance cassette in the opposite orientation to the gene. The vector was linearized and injected into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Targeted clones were injected into C57BL/6 blastocysts. Resultant chimeric mice were backcrossed to C57BL/6 for 10 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
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. One of the 27 markers on Chromosome 4 is segregating, likly due to targeted mutation. All 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||RICK-; Rip2-|
|Gene Symbol and Name||Ripk2, receptor (TNFRSF)-interacting serine-threonine kinase 2|
|Gene Synonym(s)||2210420D18Rik; 2210420D18Rik; CARD3; CARDIAK; CCK; D4Bwg0615e; D4Bwg0615e; DNA segment, Chr 4, Brigham & Women's Genetics 0615 expressed; GIG30; RICK; RIKEN cDNA 2210420D18 gene; RIP2|
|Strain of Origin||129S1/Sv-Oca2<+> Tyr<+> Kitl<+>|
|Molecular Note||The gene was disrupted by replacement of exons 2 and 3 with a neomycin resistance gene by homologous recombination. Absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis of thymocyte extracts.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
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.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
"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.