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Strain Name:

ALR/LtJ

Stock Number:

003070

Availability:

Repository- Live

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General Terms and Conditions

Strain Common Names      Alloxan Resistance;
Genes & Alleles   Cdh23;   Cdh23ahl;

Product Information

Strain Details

Type Inbred Strain
Additional information on Inbred Strains.
Mating SystemSibling x Sibling         (Female x Male)
Specieslaboratory mouse
H2 Haplotypegx
GenerationF?+16+24 (24-JAN-08)

Appearance
albino
Related Genotype: a/a Tyrc/Tyrc

Important Note
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 3 months of age.

Strain Description
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/LtJ 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.

Strain Development
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.

Gene & Allele Details

Allele Symbol Cdh23ahl
Allele Name age related hearing loss 1
Common Name(s) Cdh23753A; mdfw;
Strain of OriginC57BL/6J
Gene Symbol and Name Cdh23, cadherin 23 (otocadherin)
Chromosome 10
Gene Common Name(s) 4930542A03Rik; DFNB12; DKFZp434P2350; FLJ00233; FLJ36499; KIAA1774; KIAA1812; MGC102761; RIKEN cDNA 4930542A03 gene; USH1D; W; age related hearing loss 1; ahl; bob; bobby; bus; bustling; mdfw; modifier of deaf waddler; neuroscience mutagenesis facility, 112; neuroscience mutagenesis facility, 181; neuroscience mutagenesis facility, 252; nmf112; nmf181; nmf252; v; waltzer;
Molecular Note Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has identified an association between ahl and a G to A transition at nucleotide position 753 of Cdh23. This hypomorphic allele causes in frame skipping of exon 7 and reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129/ScJ, NOR/LtJ, A/J, C57BL/6, NOD/LyJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: C3H/HeSnJ, I/LnJ,YBR/Ei, MRL/MpJ. [J:86905]

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Alloxan Resistance and Susceptibility Strains
003072   ALS/LtJ
View Alloxan Resistance and Susceptibility Strains     (1 strain)

Strains carrying   Cdh23ahl allele
001137   129P1/ReJ
000690   129P3/J
002065   129T2/SvEmsJ
000691   129X1/SvJ
000646   A/J
000647   A/WySnJ
003072   ALS/LtJ
004502   B6;AKR-Lxl2/J
001026   BALB/cByJ
000653   BUB/BnJ
005494   C3.129S1(B6)-Grm1rcw/J
000664   C57BL/6J
004764   C57BL/6J-Cdh23v-8J/J
003129   C57BL/6J-Epha4rb-2J/J
004820   C57BL/6J-Kcne12J/J
004703   C57BL/6J-Nmf134/J
004811   C57BL/6J-nmf110/J
004812   C57BL/6J-nmf111/J
004747   C57BL/6J-nmf118/J
004656   C57BL/6J-nmf88/J
004391   C57BL/6J-Chr 13A/J/NaJ
004385   C57BL/6J-Chr 7A/J/NaJ
000662   C57BLKS/J
000667   C57BR/cdJ
000668   C57L/J
000669   C58/J
000657   CE/J
000670   DBA/1J
001140   DBA/1LacJ
000671   DBA/2J
007048   DBA/2J-Gpnmb+/SjJ
002106   KK/HlJ
000675   LG/J
000676   LP/J
000677   MA/MyJ
001976   NOD/ShiLtJ
002050   NOR/LtJ
000679   P/J
002747   SENCARB/PtJ
002335   SKH2/J
003392   STOCK Crb1rd8/J
View Strains carrying   Cdh23ahl     (41 strains)

Strains carrying other alleles of Cdh23
002756   B6.CAST-Cdh23Ahl+/Kjn
002432   B6J x B6.C-H2bm1/ByJ-Cdh23v-J/J
002552   C57BL/6J-Cdh23v-2J/J
004764   C57BL/6J-Cdh23v-8J/J
004819   C57BL/6J-Cdh23v-9J/J
005016   CByJ;B6-Cdh23v-10J/J
000275   V/LeJ
View Strains carrying other alleles of Cdh23     (7 strains)

Phenotypic Data

Mouse Phenome Database

Additional Web Information

JAX Notes, Fall 1999; 479. New Mouse Models for Diabetes and Free Radical Research.
JAX Notes, Spring 1999; 477. Control Strains for NOD/LtJ Mice in Diabetes Research.

Animal Health Reports

Room Number           FGB29

Research Applications

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

Diabetes and Obesity Research
Islet Transplantation Studies
Obesity Without Diabetes (moderate, adult onset)
Type 1 Diabetes (IDDM) Analysis Strains (Related Inbred Strains)
Type 2 Diabetes (NIDDM) (control for ALS/LtJ)

Immunology and Inflammation Research
Autoimmunity

Metabolism Research
Free Radical Research

Neurobiology Research
Vestibular and Hearing Defects (Age related hearing loss)

Research Tools
Toxicology Research (free radical research)

Sensorineural Research
Vestibular and Hearing Defects (Age related hearing loss)

Cdh23ahl related

Neurobiology Research
Vestibular and Hearing Defects (Age related hearing loss)

Sensorineural Research
Vestibular and Hearing Defects (Age related hearing loss)

References

Selected Reference(s)

Graser RT; Mathews CE; Leiter EH; Serreze DV. 1999. MHC characterization of ALR and ALS mice: respective similarities to the NOD and NON strains. Immunogenetics 49(7-8):722-6. [PubMed: 10369935]  [J:56048]

Ino T; Kawamoto Y; Sato K; Nishikawa K; Yamada A; Ishibashi K; Sekiguchi F. 1991. Selection of mouse strains showing high and low incidences of alloxan-induced diabetes. Jikken Dobutsu 40(1):61-7. [PubMed: 2007436]  [J:109927]

Mathews CE; Dunn BD; Hannigan MO; Huang CK; Leiter EH. 2002. Genetic control of neutrophil superoxide production in diabetes-resistant ALR/Lt mice. Free Radic Biol Med 32(8):744-51. [PubMed: 11937300]  [J:76108]

Mathews CE; Graser RT; Savinov A; Serreze DV; Leiter EH. 2001. Unusual resistance of ALR/Lt mouse beta cells to autoimmune destruction: role for beta cell-expressed resistance determinants. Proc Natl Acad Sci U S A 98(1):235-40. [PubMed: 11136257]  [J:66705]

Mathews CE; Leiter EH. 1999. Constitutive differences in antioxidant defense status distinguish alloxan-resistant and alloxan-susceptible mice. Free Radic Biol Med 27(3-4):449-55. [PubMed: 10468221]  [J:57552]

Sekiguchi F; Ishibashi K; Katoh H; Kawamoto Y; Ino T. 1990. Genetic profile of alloxan-induced diabetes-susceptible mice (ALS) and-resistant mice (ALR). Exp Anim 39(2):269-72. [PubMed: 2361527]  [J:109930]

Additional References

Price and Supply Information

Strain Name: ALR/LtJ
Stock Number: 003070

Price Details

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Supply Details

Standard SupplyRepository-Live. No age specifications accepted. Colony sized to produce minimal quantities (typically up to 6 mice) upon order receipt; one order per strain. Expected delivery: 1-3 months. Larger quantities or custom orders arranged upon request.
Supply Notes Usually shipped between four and six weeks of age.
This strain is included in the Mouse Mutant Resource collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below  

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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.
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