NOD.D1(B6)-Ctss^tm1Eae/RclJ

Stock number: 008524
Product name: NOD.CatS
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

This congenic NOD strain contains a neomycin cassette that deletes the cathepsin S (Ctss^tm1Eae) active site cysteine. NOD Ctss deficient mice exhibit significantly reduced diabetes onset. This model provides a tool for detailed studies to identify the molecular pathways of major lysosomal cysteine proteases, specifically cathepsin S, in immune modulation.

Detailed description

Mice homozygous for the Ctss targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Cathepsin S activity was not present in splenic cells or LPS induced B cell blasts.

Diabetes incidence in mutant mice was significantly reduced (33%) compared to heterozygous and NOD control females (69%). Histological analysis of the pancreas from non-diabetic mutant females revealed extensive insulitis. Thyroiditis scores were significantly greater while sialadenitis scores were less than NOD wild-type females.

This model provides a tool for detailed studies to identify molecular pathways of major lysosomal cysteine proteases, specifically cathepsin S, in immune modulation.

Development

The Cathepsin S (Ctss) gene (Chromosome 3, 95Mb) was disrupted via homologous recombination in DBA1-252 ES cells. The active site cysteine, was deleted by the insertion of a neomycin selection cassette. The ES cell clone was injected into C57BL/6 blastocysts (Nakagawa et al, 1999). The resulting chimeric founder's and offspring were bred to C57BL/6J prior to 10 generations of crossing to NOD and intercrossing. In 2009, the T1DR received this stock at generation N11F2.

Allele

Symbol: Ctss^tm1Eae
Name: targeted mutation 1, Eileen A Elliot
MGI accession ID: MGI:2182132
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ctss
Marker name: cathepsin S
Chromosome: 3
Strain of origin: DBA/1LacJ
Molecular note: A neomycin selection cassette replaced a 3.0kb region containing the active site residue. Functional ablation of the protein product in homozygous mutant mice was determined via an active-site labeling assay of splenocytes and LPS B cell blasts.
General note: The author (Renee LeBoeuf) has confirmed that the allele used in the reference J:153355 was incorrectly reported as Ctss^tm1Hap; the correct allele is Ctss^tm1Eae .