Cultured LPS stimulated bone marrow derived macrophages from homozygous animals secrete less IL1 beta and IL1 alpha; IL18 is undetectable when compared with hemizygous and wild-type controls. Diabetes frequency of Casp1tm1Sesh deficient animals is equivalent to NOD/Lt, heterozygote and wild-type controls. This strain is a useful model for studying the role of IL1 and IL18 cytokines in inflammatory processes relating to diabetes.
Dr. Edward Leiter, The Jackson Laboratory
Casp1tm1Sesh homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Casp1 in spleen by northern blot analysis or by RT-PCR of peritoneal exudate cells, brain, lung, heart, liver, adrenal gland, kidney, testis, and thymus (Li et al, 1995). Cultured LPS stimulated bone marrow derived macrophages from homozygous NOD.129S2(B6)- Casp1tm1Sesh /LtJ animals secrete 4-fold less IL1 beta, 30% less IL1 alpha, and IL18 is undetectable when compared with hemizygous and wild-type controls. Diabetes frequency of Casp1tm1Sesh deficient animals is equivalent to NOD/Lt, heterozygote and wild-type controls. Weanling Casp1tm1Sesh homozygous animals injected with Complete Freund's adjuvant and young pre-diabetic males treated with multiple low dose streptozotocin behave similarly to control (wild type, heterozygote, or NOD/Lt) animals (Schott et al, 2004). NOD.129S2(B6)- Casp1tm1Sesh/LtJ is a useful model for studying the role of IL1 and IL18 cytokines in inflammatory processes relating to diabetes.
A construct containing a neomycin expression cassette inserted into exon 6 of Casp1 (cloned from a 129/Sv mouse), deleting 31 bp of sequence encoding the region of the catalytic active site and rendering the sequence out of frame after the insertion, was transfected into D3 (129S2/SvPas derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. Chimeric founders were initially mated to C57BL/6 and subsequently intercrossed to generate homozygotes (Li et al, 1995). In 1998, Dr. Edward Leiter at The Jackson Laboratory received B6.129S2-Casp1tm1Sesh mice from Dr. Winnie Wong, BASF Bioresearch Corporation and backcrossed this mutation to NOD/Lt for 10 generations, subsequently intercrossing to generate homozygotes (Schott et al. 2004). In 2004, NOD.129S2(B6)- Casp1tm1Sesh /LtJ homozygous strain at N10F11 was transferred from Edward Leiter's research colony to a Jackson Laboratory distribution colony.
|Allele Name||targeted mutation 1, Tara Seshadri|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Tara Seshadri; Casp1tm1Sesh|
|Gene Symbol and Name||Casp1, caspase 1|
|Gene Synonym(s)||Caspase-1; IL1BC; interleukin 1 beta-converting enzyme; P45; Il1bc; ICE; interleukin 1 beta convertase; Il1bc; Ice|
|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 neomycin expression cassette was inserted into exon 6, deleting 31 bp of sequence encoding the region of the active site and rendering the sequence out of frame after the insertion. Northern blot analysis on spleen RNA demonstrated an absence of the normal transcript in homozygous mice, and western blot analysis showed that the protein was not expressed in peritoneal macrophages of homozygous mice. This allele was generated in ES cells that lack protein expression of Casp11 (Casp129mt).|
|Mutations Made By|| |
Dr. Edward Leiter, The Jackson Laboratory
|Allele Synonym(s)||deletion; Casp4del|
|Gene Symbol and Name||Casp4, caspase 4, apoptosis-related cysteine peptidase|
|Gene Synonym(s)||ICH-2; Casp11; Caspase-11; capase 11, apoptosis-related cysteine protease; Casp11; TX; Mih1/TX; caspase 11, apoptosis-related cysteine peptidase; ICE(rel)II; ich-3; ICEREL-II; Mih1|
|Strain of Origin||129P3/J and 129S1/SvImJ and 129S2/SvPas and 129S6/SvEvTac and 129X1/SvJ|
|Molecular Note||RT-PCR confirmed that five 129 substrains (129X1/SvJ, 129S1/SvImJ, 129S2/SvPas, 129S6/SvEvTac and 129P3/J) express a transcript that lacks exon 7 (delta110 isoform). Sequencing identified a 5 bp deletion in exon 7 that results in the fusion of exon 6 and 8, a frame-shift after proline 304 and a stop codon after 5 aberrant amino acids. This deletion is not present in C57BL/6. Western blot analysis confirmed the absence of protein expression in LPS-primed macrophage.|
A footpad injection of Complete Freund's Adjuvant (CFA) administered once at weaning will delay diabetes onset, thus extending the lifespan of breeders. A discussion on the use of Complete Freund's Adjuvant in NOD mice can be found in Current Protocols in Immunology (1997) pages 15.9.1-15.9.23 (see PDF link under Immunological protocols).
When using the ICE mouse strain in a publication, please cite the originating article(s) and include JAX stock #004947 in your Materials and Methods section.
|Homozygous for Casp1<tm1Sesh> and Homozygous for Casp4<del>, 1 pair minimum|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.