Overview

Also Known As:NOD.Catl, NOD.CatL

This congenic NOD strain contains a neomycin cassette disruption in exon 3 of cathepsin L (Ctsl^tm1Cptr). 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.

Donating Investigator

Dr. Renee C LeBoeuf, Universtiy of Washington

Genetic overview

Genetic Background	Generation

Ctsl^tm1Cptr

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ctsl	cathepsin L

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Research Applications

Diabetes and Obesity Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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-Ctsl^tm1Cptr 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.

Development

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.

Control Suggestions

001976 NOD/ShiLtJ

Additional Information

Considerations for Choosing Controls

Genetics

Ctsl^tm1Cptr

Allele Symbol: Ctsl^tm1Cptr

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 Ctsb^tm1Jde, 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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
  - resistant
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - Type 1 Diabetes

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ctsl^tm1Cptr/Ctsl^tm1Cptr
NOD.129P2-Ctsl

digestive/alimentary phenotype

salivary gland inflammation
- sialadenitis is observed in both diabetic and nondiabetic mice at 6 months of age, however, number of lesions observed is less than number found in NOD mice (6.5 vs. 12-20)

endocrine/exocrine gland phenotype

salivary gland inflammation
- sialadenitis is observed in both diabetic and nondiabetic mice at 6 months of age, however, number of lesions observed is less than number found in NOD mice (6.5 vs. 12-20)

hematopoietic system phenotype

decreased CD4-positive, alpha beta T cell number
- number of CD4+ T cells is 3-fold reduced in thymus and lymph nodes as compared to NOD control

increased regulatory T cell number
- homozygotes exhibit a 2-fold increase in Foxp3-expressing T cells in comparison to heterozygotes

immune system phenotype

decreased CD4-positive, alpha beta T cell number
- number of CD4+ T cells is 3-fold reduced in thymus and lymph nodes as compared to NOD control

decreased susceptibility to autoimmune diabetes
- adoptive transfer of GITR^hi-depleted Treg cells into NOD-Prkdc^scid host results in a diabetes incidence of 45.5%
- mice exhibit a complete resistance to diabetes

increased regulatory T cell number
- homozygotes exhibit a 2-fold increase in Foxp3-expressing T cells in comparison to heterozygotes

salivary gland inflammation
- sialadenitis is observed in both diabetic and nondiabetic mice at 6 months of age, however, number of lesions observed is less than number found in NOD mice (6.5 vs. 12-20)

Genotype: Ctsl^tm1Cptr/Ctsl⁺
NOD.129P2-Ctsl

endocrine/exocrine gland phenotype

insulitis
- insulitis scores for diabetic animals are similar to diabetic NOD controls

homeostasis/metabolism phenotype

hyperglycemia
- 55% of female mice exhibit blood glucose levels of greater than 250 mg/dl between 4-6 months of age as compared to 69% of NOD controls

immune system phenotype

decreased susceptibility to autoimmune diabetes
- 55% of female mice exhibit blood glucose levels of greater than 250 mg/dl between 4-6 months of age as compared to 69% of NOD controls
- adoptive transfer of GITR^hi-depleted Treg cells into NOD-Prkdc^scid host results in a diabetes incidence of 41.7%

insulitis
- insulitis scores for diabetic animals are similar to diabetic NOD controls

References

Additional - Ctsl^tm1Cptr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Cstl
- Genotyping resources and troubleshooting
Breeding Considerations

Recommended breeding scheme is to mate heterozygous females with homozygous males.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Cstl<tm1Cptr>

Related Products and Services

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

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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.

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Also Known As:NOD.Catl, NOD.CatL

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Ctsltm1Cptr

Allele Symbol: Ctsltm1Cptr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ctsltm1Cptr/Ctsltm1CptrNOD.129P2-Ctsl

digestive/alimentary phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Ctsltm1Cptr/Ctsl+NOD.129P2-Ctsl

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional - Ctsltm1Cptr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ctsl^tm1Cptr

Allele Symbol: Ctsl^tm1Cptr

Genotype: Ctsl^tm1Cptr/Ctsl^tm1Cptr
NOD.129P2-Ctsl

Genotype: Ctsl^tm1Cptr/Ctsl⁺
NOD.129P2-Ctsl

Additional - Ctsl^tm1Cptr related