This strain, relevant to studies of inflammation and cell death, carries a knockout allele of the Casp1 gene as well as an incidental Casp4 deficiency.
Dr. Richard A. Flavell, Yale University School of MedicineRead More +
Caspase 1 (also known as interleukin-1beta converting enzyme or ICE) knockout mice lack part of exons 6 and 7 of the Casp1 gene and do not process pro-IL-1beta (IL1B) or pro-IL-18 (IL18) into their mature forms. Therefore, stimulation of CASP1-deficient monocytes by activators of multiple pattern recognition receptors that form inflammasomes with CASP1 (including Nlrp3 and Nlrc4) fail to secrete mature IL1B or IL18. In addition, secretion of IL-1alpha (IL1A) is reduced. Caspase-1 is involved in particular cell death pathways including pyroptosis, and caspase-1 deficient cells demonstrate reduced lysis upon infection with certain pathogens.
It has recently been confirmed that these mice are de facto Casp1/Casp4(formerly called caspase 11) double knockout mice. This is resultant from the dysfunctional nature of the naturally occuring 129 Casp4 allele. These Casp1 knockout mice were produced in embryonic stem (ES) cells on a 129S2 background.
Homozygous Casp1 targeted mutant mice are viable, fertile, and show no gross abnormalities in appearance, body weight or organ size for at least the first 16 weeks of life. Homozygotes are born at predicted Mendelian frequencies and the absence of mRNA was confirmed by RT-PCR analysis.
A 2.5 kb EcoRI-HindIII fragment containing caspase 1 exons 4-6 and a 1.3 kb EcoRI-SmaI fragment containing exons 8-10 were subcloned with the neomycin resistance gene cassette in a thymidine kinase gene-expressing plasmid to generate the targeting vector. The vector was linearized and introduced into 129S2/SvPas-derived embryonic stem (ES) cells by electroporation. 63 clones resistant to G418 and Gancyclovir were screened by PCR using and exon 10 primer and a neo cassette specific primer. One correctly targeted clone was confirmed by Southern blot analysis. Chimeric mice were generated from the targeted ES cells and chimeras bred to germline. The donating investigator reported that the progeny were backcrossed at least 10 generation on C57BL/6N background (see SNP note below).
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, 2 of 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 mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Richard Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Casp1-; ICE-; caspase-1-|
|Gene Symbol and Name||Casp1, caspase 1|
|Gene Synonym(s)||Caspase-1; ICE; IL1BC; Ice; Il1bc; Il1bc; P45; interleukin 1 beta convertase; interleukin 1 beta-converting enzyme|
|Strain of Origin||129S2/SvPas|
|General Note||The ES cells used to generate this allele contain the linked Casp4del truncated allele that fails to produce a functional Casp4. Phenotypes associated with this allele may be affected by the presence of the Caspdel allele. J:193522|
|Molecular Note||A genomic fragment containing part of exon 6 and exon 7 was replaced with a neomycin selection cassette. RT-PCR analysis on samples derived from homozygous mice demonstrated that no detectable transcript was produced from this allele.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
|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.
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.
"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.