This strain is homozygous for Cdh23ahl, the age related hearing loss 1 mutation, which on this background results in progressive hearing loss with onset prior to three months of age.
ALS/LtJ (Stock No. 003072) and ALR/LtJ inbred strains are of interest to investigators across a wide range of scientific disciplines including type 1 and type 2 diabetes, obesity, metabolism and toxicology research. Treatment of alloxan or streptozotocin causing pancreatic beta cell destruction, leads to severe hyperglycemia and hypoinsulinemia in ALS/LtJ mice. ALR/LtJ mice are resistant to these toxins. ALR/LtJ mice are of particular interest to investigators studying the immunogenetics of NOD/ShiLtJ mice in that the ALR/LtJ MHC haplotype (H2gx) is a variant of the diabetogenic NOD H2g7 haplotype. The (H2gx) haplotype is identical to the H2g7 haplotype from the H2-K end of the complex through the class II and class III region distal to Hsp70. However, at the distal H2-D end of the complex, ALR/LtJ mice have a rare H2-Dgx allele. Despite the similarities to the NOD/ShiLtJ mice, ALR/LtJ mice do not develop type 1 insulin dependent diabetes and thus provide an important control strain for NOD/ShiLtJ. ALR/Lt islets are unusually resistant in vitro to beta cell selective toxins known to generate free radicals (alloxan and streptozotocin). In addition, ALR/Lt islets are resistant to cytokine-mediated destruction. This resistance is correlated with an ALR strain-specific systematic elevation of enzymes and molecules associated with dissipation of free radicals. ALR/Lt mice of both sexes not treated with alloxan exhibit normal glucose tolerance, but gain weight rapidly, with females exhibiting male-like weight at 50 weeks of age. Understanding the genetic basis for the resistance of ALR mice to free radical mediated stressors, like alloxan and streptozotocin, as well as to immune system mediated stress, should prove valuable to pharmacologists interested in a variety of autoimmune and other diseases in which reactive oxygen species are associated with pathology.
Alloxan is a pancreatic beta cell-selective toxin that induces diabetes in rodents by generating cytotoxic free radicals. The ALR (alloxan-induced diabetes-resistant) inbred strain was created in Japan by selective inbreeding of Crj:CD-1 (ICR) mice with selection for resistance to diabetes development after administration of alloxan at doses representing the ED50 for the original Crj:CD-1 strain (45 mg/kg in males, 47 mg/kg in females). These dosages are lower than what is necessary to elicit a strong diabetogenic response in most inbred strains, typically 60mg/kg. After a litter was born and weaned, the parents and some of the progeny were alloxan-treated to select for low versus high [ALS (alloxan-induced diabetes-susceptible)] incidence lines based on blood glucose levels at 7 days post treatment. ALS and ALR inbred strains were obtained from Japan by Dr. EH Leiter (Lt) at The Jackson Laboratory in 1996. ALS/Lt and ALR/Lt mice were transferred to the production colony in 1998. Genome wide scan demonstrated that ALR/LtJ mice are not only closely related to ALS/Lt mice, but also to two other ICR-derived inbred strains selected for diabetes susceptibility and distributed by The Jackson Laboratory: NOD/LtJ and NON/LtJ.
|Allele Name||age related hearing loss 1|
|Allele Synonym(s)||Cdh23753A; mdfw|
|Gene Symbol and Name||Cdh23, cadherin 23 (otocadherin)|
|Strain of Origin||multiple strains|
|Molecular Note||Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G to A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870). This hypomorphic allele changes splice donor site G-GT to A-GT, causing frame skipping of exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.|
|Allele Name||mutation 2|
|Gene Symbol and Name||mt-Tr, mitochondrially encoded tRNA arginine|
|Strain of Origin||various|
|General Note||This polymorphism is present in ALR/Lt, NOD/ShiLtDvs, and SKH2/J. A variant with 10 adenines is found in A/J, ALS/Lt, NOD/ShiLtJ and NZB/B1NJ.|
|Molecular Note||The adenine repeat in the D stem is polymorphic with 9 adenines in this allele.|
"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.