This congenic NOD strain contains a neomycin cassette that disrupts exon 4 of cathepsin B (Ctsbtm1Jde). NOD Ctsb deficient mice exhibit modestly delayed diabetes onset. This model provides a tool for detailed studies to identify the molecular pathways of major lysosomal cysteine proteases, specifically cathepsin B, in immune modulation.
Dr. Renee C LeBoeuf, Universtiy of Washington
Mice homozygous for the Ctsb targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Northern blot analysis of kidney total RNA indicates a lack of transcript in homozygous mutant mice. An absence of Ctsb protein in homozygous mutant mice was determined by Western blot analysis of kidney lysosomal protein extracts. The proteolytic activity of the endogenous protein was found to be absent using an assay involving liver lysosomal extracts, obtained from homozygous mutant mice, and a fluorogenic substrate (Halangk et al. 2000).
The donating investigator indicates that the diabetes incidence in homozygous mutant NOD mice is significantly reduced (28%) compared to wildtype NOD (69%), while heterozygous mice are modestly protected from diabetes (50%) at six months of age. Histological analysis of the pancreas from non-diabetic homozygous mice indicate that insulitis is present but at much lower levels than in diabetic homozygous mice. Heterozygous mice had severe insulitis, indicating that the loss of one Ctsb allele is associated with delayed diabetes onset. Thyroiditis and sialadentis scores of mutant and NOD mice are equivalent. Data collected indicates that the loss of Cathepsin B delays but does not halt diabetes onset.
This model provides a tool for detailed studies focused on the identification of the molecular pathways of major lysosomal cysteine proteases, specifically cathepsin B, in immune modulation.
The Cathepsin B gene, located on Chromosome 14, 63.7Mb, was disrupted via homologous recombination in 129P2/OlaHsd-derived, E14.1 ES cells. A neomycin cassette was inserted into a BglII site in exon 4; which introduced a premature stop codon into the open reading frame of the Ctsb gene. The resulting ES cell clone was injected into C57BL/6 blastocysts. The chimeric founder's offspring were bred to C57BL/6J prior to 10 generations of crossing to NOD and intercrossing. Marker assisted analysis indicate 19 known Idd loci which are of NOD origin. In 2008, the T1DR received this strain at generation N11F2.
|Allele Name||targeted mutation 1, Jan Deussing|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CTSB-; Cat B-; CathB-; Ctsb-|
|Gene Symbol and Name||Ctsb, cathepsin B|
|Gene Synonym(s)||APPS; CB; CPSB|
|Strain of Origin||129P2/OlaHsd|
|General Note||in combination with Ctsltm1Cptr, double homozygous mutant have some similarities but distinct phenotypic characteristics compared to the human syndrome: neuronal ceroid lipofuscinoses (NLCs)|
|Molecular Note||A neomycin selection cassette was inserted into a BglII site in exon 4. Northern blot analysis of total RNA showed a lack of transcript in homozygous mutant mice. An absence of protein in homozygous mutant mice was determined by Western blot analysis of kidney lysosomal protein extracts. The proteolytic activity of the endogenous protein was found to be absent using an assay involving liver lysosomal extracts obtained from of homozygous mutant mice and a fluorogenic substrate.|
|Mutations Made By|| |
Dr Jan Deussing, Max-Planck-Institute of Psychiatrie
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.