This congenic NOD strain contains a neomycin cassette disruption in exon 3 of cathepsin L (Ctsltm1Cptr). NOD Ctsl deficient mice exhibit defective CD4+T cell development and express Foxp3 on CD4+ T cells at a 2 fold higher frequency than controls. Homozygous mice are insulitis and diabetes resistant. This model provides a tool for detailed studies to identify the molecular pathways of major lysosomal cysteine proteases, specifically cathepsin L, in immune modulation.
Dr. Renee C LeBoeuf, Universtiy of Washington
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ctsl | cathepsin L |
Mice homozygous for this Ctsl targeted mutation are viable, normal in size, and do not display any behavioral abnormalities. Western blot analysis failed to detect any signal in kidneys of homozygous mutant mice. No Ctsl enzymatic activity was detected in the kidney using a synthetic substrate. Donating investigator reports that homozygous females are infertile; while homozygous males breed well. As reported in the B6-Ctsltm1Cptr by Roth et al. 2000, the vibrissae of NOD congenic mutant mice have not penetrated the epidermis at birth and the first emergence of fur is delayed by approximately two days. Beginning around three weeks of age NOD mutant mice begin to lose their fur beginning at the head and progressing toward the tail region. Mature mutant mice are always partially devoid of fur. Unlike the observations of Roth et al. there appears to be no distortion of the the expected rates of homozygous NOD congenic mice weaned. Similar to Maehr et al. 2005, no throiditis, sialadenitis, diabetes or insulitis was detected in NOD.Ctsl deficient females aged to 10 months (Hsing et al, 2009). Ctsl deficient mice exhibit defective CD4+T cell development leading to a reduced CD4:CD8 ratio. CD4+T cells if naive NOD.Ctsl deficient mice exhibit Foxp3 expression at 2 fold higher frequency than wildtype controls (Hsing et al, 2009).
This model provides a tool for detailed studies to identify the molecular pathways of major lysosomal cysteine proteases, specifically cathepsin L in immune modulation.
The Cathepsin L (Ctsl) gene was disrupted via homologous recombination in 129P2/OlaHsd-derived, E14.1 ES cells. A neomycin cassette was inserted into a NcoI site in exon 3 using a SalI linker containing stop codons in all reading frames of the Ctsl gene. The ES cell clone was injected into C57BL/6 blastocysts. The resulting chimeric founder's offspring were bred to C57BL/6J prior to 10 generations of crossing to NOD and intercrossing. Marker assisted analysis indicates 19 known Idd loci are of NOD origin. In 2008, the T1DR received this strain at generation N11F2.
Allele Name | targeted mutation 1, Christoph Peters |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Cat L-; catL-; CL-; ctsl-; L- |
Gene Symbol and Name | Ctsl, cathepsin L |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 13 |
General Note | In combination with Ctsbtm1Jde, double homozygous mutant have some similarities but distinct phenotypic characteristics compared to the human syndrome: Neuronal Ceroid Lipofuscinoses (NLCs) |
Molecular Note | Insertion of a neomycin resistance cassette into exon 3. Northern and Western analysis failed to detect any signal in homozygous mutant mice. No Ctsl enzymatic activity was detected using a synthetic substrate. |
Recommended breeding scheme is to mate heterozygous females with homozygous males.
When using the NOD.CatL mouse strain in a publication, please cite the originating article(s) and include JAX stock #008352 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Cstl<tm1Cptr> |
Frozen Mouse Embryo | NOD.129P2(B6)-Ctsl<tm1Cptr>/RclJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | NOD.129P2(B6)-Ctsl<tm1Cptr>/RclJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | NOD.129P2(B6)-Ctsl<tm1Cptr>/RclJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | NOD.129P2(B6)-Ctsl<tm1Cptr>/RclJ Frozen Embryo | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.