Overview

Also Known As:Alloxan Susceptibility

ALS/LtJ and ALR/LtJ (Stock No. 003070) inbred strains are useful for a wide range od studies 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. Alloxan-untreated ALS/Lt males exhibit impaired glucose tolerance when tested by intraperitoneal administration of glucose, and become hyperinsulinemic . ALS/LtJ mice contain genes predisposing to both experimentally-induced type 1 and spontaneously-developing type 2 diabetes mellitus. ALS/Lt mice exhibit significantly lower antioxidant defenses than do ALR/Lt. ALS/Lt is a useful control strain for comparing inbred strain susceptibility to free radical-mediated damage.

Genetic overview

Genetic Background	Generation

View Genetics

Research Applications

Diabetes and Obesity Research
Sensorineural Research
Neurobiology Research
Metabolism Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Important Note

This strain is homozygous for Cdh23^ahl, the age related hearing loss 1 mutation, which on this background results in progressive hearing loss with onset prior to three months of age and for Gnat2^cpfl3, cone photoreceptor function loss 3, which affects bright light (photopic) vision.

Detailed 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 weeks 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 H2^nb1 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 weeks 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 nine to 32 weeks 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.

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.

Selected References

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):722-6PubMed: 10369935 MGI: 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:S125-9PubMed: 14749277 MGI: 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):744-51PubMed: 11937300 MGI: J:76108
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):449-55PubMed: 10468221 MGI: J:57552
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):2189-96PubMed: 10535453 MGI: J:109893
Petkov PM; Cassell MA; Sargent EE; Donnelly CJ; Robinson P; Crew V; Asquith S; Haar RV; Wiles MV. 2004. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902-11PubMed: 15081119 MGI: J:89298
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):269-72PubMed: 2361527 MGI: 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):503-8PubMed: 7489831 MGI: J:25653

View All References

Genetics

Cdh23^ahl

Allele Symbol: Cdh23^ahl

Allele Name	age related hearing loss 1
Allele Type	Spontaneous
Allele Synonym(s)	Cdh23^753A; mdfw
Gene Symbol and Name	Cdh23, cadherin 23 (otocadherin)
Gene Synonym(s)
Strain of Origin	multiple strains
Chromosome	10
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.

Gnat2^cpfl3

Allele Symbol: Gnat2^cpfl3

Allele Name	cone photoreceptor function loss 3
Allele Type	Spontaneous
Allele Synonym(s)	no cones
Gene Symbol and Name	Gnat2, guanine nucleotide binding protein, alpha transducing 2
Gene Synonym(s)
Strain of Origin	various
Chromosome	3
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) The allele has also been reported in NMRI and CD1 (Lluis Montoliu, J:212307)
Molecular Note	A single nucleotide substitution of G to A at coding nucleotide 598 in exon 6. This mutation converts codon 200 from aspartic acid to asparagine (p.D200N).

mt-Tr^m1

Allele Symbol: mt-Tr^m1

Allele Name	mutation 1
Allele Type	Spontaneous
Allele Synonym(s)	10A
Gene Symbol and Name	mt-Tr, mitochondrially encoded tRNA arginine
Gene Synonym(s)
Strain of Origin	various
Chromosome	MT
General Note	This polymorphism is present in A/J, NZB/B1NJ, ALS/Lt and NOD/ShiLtJ. A variant with 9 adenines is found in NOD/ShiLtDvs, ALR/Lt and SKH2/J.
Molecular Note	The adenine repeat in the D stem is polymorphic with 10 adenines in this allele.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

achromatopsia 4

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Hyperinsulinemia
  - males; spontaneous, alloxan untreated
- Type 1 Diabetes (IDDM)
  - males: alloxan induced
- Type 2 Diabetes (NIDDM)
  - males: spontaneous, alloxan untreated
  - males
- Hyperglycemia
  - alloxan induced
- Insulin Resistance
  - males; spontaneous, alloxan untreated
- Hypoinsulinemia
  - alloxan induced
- Type 1 Diabetes (IDDM) Analysis Strains
  - Related Inbred Strains
- Obesity With Diabetes
  - moderate, adult onset
Neurobiology Research
- Hearing Defects
  - Age related hearing loss
Sensorineural Research
- Hearing Defects
  - Age related hearing loss
Metabolism Research
- Free Radical Research
Research Tools
- Toxicology Research
  - free radical research

Genotype: Gnat2^cpfl3 related

Sensorineural Research
- Eye Defects

Genotype: Cdh23^ahl related

Neurobiology Research
- Hearing Defects
  - Age related hearing loss
Sensorineural Research
- Hearing Defects
  - Age related hearing loss

Mammalian Phenotype Terms by Genotype

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

Genotype: Gnat2^cpfl3/Gnat2^cpfl3
ALS/LtJ

cardiovascular system phenotype

abnormal retinal vasculature morphology
- dilated retinal veins and slightly constricted arterioles are observed in 8 month old mice

nervous system phenotype

abnormal photoreceptor outer segment morphology
- outer segments are vacuolated by 27 weeks of age

abnormal retinal cone cell morphology
- reduced labeling for alpha-transducin in cone outer segments as determined by immunocytochemistry, however, PNA staining reveals a normal number of cone outer segments

vision/eye phenotype

abnormal cone electrophysiology
- photopic responses are 25% of normal by 4 weeks of age and completely diminished by 9 months
- scotopic (rod) responses show some diminution, but are near normal by 9 months of age

abnormal photoreceptor outer segment morphology
- outer segments are vacuolated by 27 weeks of age

abnormal retinal cone cell morphology
- reduced labeling for alpha-transducin in cone outer segments as determined by immunocytochemistry, however, PNA staining reveals a normal number of cone outer segments

abnormal retinal vasculature morphology
- dilated retinal veins and slightly constricted arterioles are observed in 8 month old mice

Phenotype Information

References

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):722-6PubMed: 10369935 MGI: 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:S125-9PubMed: 14749277 MGI: 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):744-51PubMed: 11937300 MGI: J:76108
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):449-55PubMed: 10468221 MGI: J:57552
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):2189-96PubMed: 10535453 MGI: J:109893
Petkov PM; Cassell MA; Sargent EE; Donnelly CJ; Robinson P; Crew V; Asquith S; Haar RV; Wiles MV. 2004. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83(5):902-11PubMed: 15081119 MGI: J:89298
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):269-72PubMed: 2361527 MGI: 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):503-8PubMed: 7489831 MGI: J:25653

Additional - Cdh23^ahl related

Additional - Gnat2^cpfl3 related

Additional - mt-Tr^m1 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- albino
  Related Genotype: a/a Tyr^c/Tyr^c
Citation
When using the ALS/LtJ mouse strain in a publication, please include JAX stock #003072 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

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Genotype

Price

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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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