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Strain Name:

ALS/LtJ

Stock Number:

003072

Availability:

Repository- Live

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General Terms and Conditions

Strain Common Names      Alloxan Susceptibility;
Genes & Alleles   Cdh23;   Cdh23ahl;   Gnat2;   Gnat2cpfl3;

Product Information

Strain Details

Type Inbred Strain
Additional information on Inbred Strains.
Mating SystemSibling x Sibling         (Female x Male)
Specieslaboratory mouse
H2 Haplotypenb1
GenerationF?+14+19 (21-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 and for Gnat2cpfl3, cone photoreceptor function loss 3, which affects bright light (photopic) vision.

Strain Description
ALS/LtJ and ALR/LtJ (Stock No. 003070) 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. By 34 wk of age, both untreated ALS/Lt and ALR/Lt males fed a 6% fat-containing chow diet attain a mean body weight of around 50 grams. Genome wide scan comparison shows that ALS/LtJ mice are more closely related to NON/ShiLtJ mice (they share the H2nb1 haplotype) than to NOD/ShiLtJ. Like two other ICR-derived inbred strains selected in Japan (NON and NSY), alloxan-untreated ALS/Lt males exhibit impaired glucose tolerance when tested by intraperitoneal administration of glucose. However, unlike NON/ShiLt males, which exhibit impaired glucose tolerance in the presence of low plasma insulin concentrations, alloxan-untreated ALS/LtJ males become hyperinsulinemic by 10 wk of age and maintain hyperinsulinemia as they age. Four untreated males and three females in a research colony have spontaneously developed type 2 diabetes between 9-32 wk of age (EH Leiter, unpublished observations). ALS/LtJ mice thus contain genes predisposing to both experimentally-inducedtype 1 and spontaneously-developing type 2 diabetes mellitus. Since ALS/Lt mice exhibit significantly lower antioxidant defenses than do ALR/Lt, yet the two strains are closely related, ALS/Lt is a useful control strain for comparing inbred strain susceptibility to free radical-mediated damage.

Strain Development
Alloxan is a pancreatic beta cell-selective toxin that induces diabetes in rodents by generating cytotoxic free radicals. The ALS (alloxan-induced diabetes-susceptible) inbred strain was created in Japan by selective inbreeding of Crj:CD-1 (ICR) mice with selection for susceptibility 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 high versus low [ALR (alloxan-induced diabetes-resistant)] 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.

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]
 
Allele Symbol Gnat2cpfl3
Allele Name cone photoreceptor function loss 3
Common Name(s) Gnat2;
Strain of Originvarious
Gene Symbol and Name Gnat2, guanine nucleotide binding protein, alpha transducing 2
Chromosome 3
Gene Common Name(s) ACHM4; AW490837; GNATC; Gnat-2; Gt-2; Tcalpha; expressed sequence AW490837;
General Note This allele has been detected in the following strains either by genotyping or complementation testing: ALS/LtJ, SENCARA/PtJ, SENCARB/PtJ, SENCARC/PtJ, PN/nBSwUmabJ. (J:122428)

Phenotypic Similarity to Human Syndrome in Orthologous Human Gene: OMIM +139340 ACHROMATOPSIA 4.

Molecular Note A single nucleotide substitution of G to A at position 598 in exon 6. This mutation converts codon 200 from apartic acid to asparagine. [J:122428]

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Alloxan Resistance and Susceptibility Strains
003070   ALR/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
003070   ALR/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)

View Strains carrying   Gnat2cpfl3     (14 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           FGB27

Research Applications

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

Diabetes and Obesity Research
Hyperglycemia (alloxan induced)
Hyperinsulinemia (males; spontaneous, alloxan untreated)
Hypoinsulinemia (alloxan induced)
Insulin Resistance (males; spontaneous, alloxan untreated)
Obesity With Diabetes (moderate, adult onset)
Type 1 Diabetes (IDDM) (males: alloxan induced)
Type 1 Diabetes (IDDM) Analysis Strains (Related Inbred Strains)
Type 2 Diabetes (NIDDM) (males: spontaneous, alloxan untreated)

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]

Mathews CE; Bagley R; Leiter EH. 2004. ALS/Lt: a new type 2 diabetes mouse model associated with low free radical scavenging potential. Diabetes 53 Suppl 1:S125-9. [PubMed: 14749277]  [J:88014]

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; Leiter EH. 1999. Resistance of ALR/Lt islets to free radical-mediated diabetogenic stress is inherited as a dominant trait. Diabetes 48(11):2189-96. [PubMed: 10535453]  [J:109893]

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]

Ueda H; Ikegami H; Yamato E; Fu J; Fukuda M; Shen G; Kawaguchi Y; Takekawa K; Fujioka Y; Fujisawa T; Nakagawa Y; Hamada Y; Shibata M; Ogihara T. 1995. The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity. Diabetologia 38(5):503-8. [PubMed: 7489831]  [J:25653]

Additional References

Price and Supply Information

Strain Name: ALS/LtJ
Stock Number: 003072

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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