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

Stock number: 005346
Product name: NOD-IL1-10^null/Casp1^null
Research areas: Cancer Research, Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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

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.

Allele

Symbol: Casp1^tm1Sesh
Name: targeted mutation 1, Tara Seshadri
MGI accession ID: MGI:1927822
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Casp1
Marker name: caspase 1
Chromosome: 9
Strain of origin: 129S2/SvPas
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).
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

Allele

Symbol: Il10^tm1Cgn
Name: targeted mutation 1, University of Cologne
MGI accession ID: MGI:1857199
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il10
Marker name: interleukin 10
Chromosome: 1
Strain of origin: 129P2/OlaHsd
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.

Allele

Symbol: Casp4^del
Name: deletion
MGI accession ID: MGI:5473345
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Casp4
Marker name: caspase 4, apoptosis-related cysteine peptidase
Chromosome: 9
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.