JAX Mouse Strain Datasheet - 005346

NOD.Cg-Il10^tm1Cgn Casp1^tm1Sesh Casp4^del/LtJ

Stock No:: 005346 |; NOD-IL1-10^null/Casp1^null

Cryo Recovery

Overview

Also Known As: NOD-IL1-10^null/Casp1^null

These mice carry a double knock-out along with a deletion; they develop type 1 diabetes and are susceptible to colitis.

Donating Investigator

Dr. Edward Leiter, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
001289 NOD/ShiLt

Casp1^tm1Sesh

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Casp1	caspase 1

Casp4^del

Allele Type	Gene Symbol	Gene Name
Spontaneous	Casp4	caspase 4, apoptosis-related cysteine peptidase

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il10	interleukin 10

Research Applications

Cancer Research
Diabetes and Obesity Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Research Tools
Hematological Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Il10 and Casp1 targeted mutations are viable and fertile when housed under SPF conditions. NOD/Lt mice deficient for both of these genes develop type 1 diabetes at a rate equivalent to the parental strains. The Il10 targeted mutation also renders this NOD/Lt stock susceptible to colitis (although not as severe as other strains of Il10 deficient mice) when maintained under standard housing conditions.

Development

For details related to the construction of each allele, please refer to the entries for strains 004947 and 004266. NOD.Il10 homozygous mice were crossed to NOD.Casp1 homozygous mice prior to making homozygous for both alleles. In 2006, the T1DR received double homozygous mice at generation F16.

Control Suggestions

None Available

Additional Information

Considerations for Choosing Controls

Genetics

Casp1^tm1Sesh

Allele Symbol: Casp1^tm1Sesh

Allele Name	targeted mutation 1, Tara Seshadri
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Casp1 -; Casp1^-/Casp11^129mt; Caspase-1-; ICE -; casp-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
Chromosome	9
General Note	The ES cells used to generate this allele contain the linked Casp4^del truncated allele that fails to produce a functional Casp4. Phenotypes associated with this allele may be affected by the presence of the Casp^del 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 (Casp^129mt).
Mutations Made By	Dr. Edward Leiter, The Jackson Laboratory

Casp4^del

Allele Symbol: Casp4^del

Allele Name	deletion
Allele Type	Spontaneous
Allele Synonym(s)	Casp¹²⁹
Gene Symbol and Name	Casp4, caspase 4, apoptosis-related cysteine peptidase
Gene Synonym(s)	Casp11; Casp11; Caspase-11; ICE(rel)II; ICEREL-II; ICH-2; Mih1; Mih1/TX; TX; capase 11, apoptosis-related cysteine protease; caspase 11, apoptosis-related cysteine peptidase; ich-3
Strain of Origin	129P3/J and 129S1/SvImJ and 129S2/SvPas and 129S6/SvEvTac and 129X1/SvJ
Chromosome	9
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.

Il10^tm1Cgn

Allele Symbol: Il10^tm1Cgn

Allele Name	targeted mutation 1, University of Cologne
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	IL-10 KO; IL-10-; IL-10^KO; IL-10KO; Il10-; Il10^tmCgn
Gene Symbol and Name	Il10, interleukin 10
Gene Synonym(s)	CSIF; GVHDS; IL-10; IL10A; IL10X; Il-10; TGIF; cytokine synthesis inhibitory factor
Strain of Origin	129P2/OlaHsd
Chromosome	1
Molecular Note	A 500 bp genomic fragment containing codons 5-55 was replaced with a linker containing a termination codon followed by a neomycin cassette. A termination codon was also introduced into exon 3. No IL10 activity was detectable by ELISA assays in supernatants of in vitro cultures of Con A-stimulated splenic T cells derived from homozygous mice following infection with the nematode N. brasiliensis.
Mutations Made By	Dr. Ralf Kuhn, University of Cologne

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Cancer Research
- Growth Factors/Receptors/Cytokines
Diabetes and Obesity Research
- Type 1 Diabetes (IDDM) Analysis Strains
  - NOD Congenics with Mutations Affecting Cytokine Production by Autoreactive T Cells
- Type 1 Diabetes (IDDM)
  - Congenics with mutations affecting cytokine production by autoreactive T cells
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
  - control strain
Internal/Organ Research
- Gastrointestinal Defects
  - colitis

Genotype: Casp1^tm1Sesh related

Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B cell defects
Research Tools
- Diabetes and Obesity Research

Genotype: Il10^tm1Cgn related

Cancer Research
- Growth Factors/Receptors/Cytokines
Hematological Research
- Anemia, Iron Deficiency and Transport Defects
  - hemolytic
- Immunological Defects
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- Growth Factors/Receptors/Cytokines
- Immunodeficiency
- Inflammation
  - Inflammatory bowel disease

References

Additional - Casp1^tm1Sesh related

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Csoka B; Nemeth ZH; Toro G; Idzko M; Zech A; Koscso B; Spolarics Z; Antonioli L; Cseri K; Erdelyi K; Pacher P; Hasko G. 2015. Extracellular ATP protects against sepsis through macrophage P2X7 purinergic receptors by enhancing intracellular bacterial killing. FASEB J 29(9):3626-37. PubMed: 26060214 MGI: J:225524
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Additional - Casp4^del related

Aachoui Y; Leaf IA; Hagar JA; Fontana MF; Campos CG; Zak DE; Tan MH; Cotter PA; Vance RE; Aderem A; Miao EA. 2013. Caspase-11 protects against bacteria that escape the vacuole. Science 339(6122):975-8. PubMed: 23348507 MGI: J:193387
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Additional - Il10^tm1Cgn related

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Yang Z; Zhang X; Darrah PA; Mosser DM. 2010. The Regulation of Th1 Responses by the p38 MAPK. J Immunol 185(10):6205-13. PubMed: 20937847 MGI: J:165637
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Also Known As: NOD-IL1-10null/Casp1null

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Casp1tm1Sesh

Allele Symbol: Casp1tm1Sesh

Casp4del

Allele Symbol: Casp4del

Il10tm1Cgn

Allele Symbol: Il10tm1Cgn

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Genotype: Casp1tm1Sesh related

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Also Known As: NOD-IL1-10^null/Casp1^null

Casp1^tm1Sesh

Allele Symbol: Casp1^tm1Sesh

Casp4^del

Allele Symbol: Casp4^del

Il10^tm1Cgn

Allele Symbol: Il10^tm1Cgn

Genotype: Casp1^tm1Sesh related

Genotype: Il10^tm1Cgn related

Additional - Casp1^tm1Sesh related

Additional - Casp4^del related

Additional - Il10^tm1Cgn related