Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Inbred Strain; Additional information on Inbred Strains. Visit our online Nomenclature tutorial. Species laboratory mouse H2 Haplotype gx Generation F?+16+8p (26-DEC-04) Generation Definitions

Appearance
albino
Related Genotype: a/a Tyr^c/Tyr^c

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.

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/ShiLtJ mice in that the ALR/LtJ MHC haplotype (H2^gx) is a variant of the diabetogenic NOD H2^g7 haplotype. The (H2^gx) haplotype is identical to the H2^g7 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-D^gx 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.

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.

Related Strains

Alloxan Resistance and Susceptibility Strains

003072

ALS/LtJ

View Alloxan Resistance and Susceptibility Strains     (1 strain)

Strains carrying   Cdh23^ahl allele

001137	129P1/ReJ
000690	129P3/J
000691	129X1/SvJ
000646	A/J
000647	A/WySnJ
003072	ALS/LtJ
004502	B6;AKR-Lxl2/GrsrJ
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/GrsrJ
004820	C57BL/6J-Kcne12J/J
004703	C57BL/6J-Kcnq2Nmf134/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
010614	CBACa.B6-Cdh23ahl/Kjn
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   Cdh23^ahl     (41 strains)

Strains carrying   mt-Tr^m2 allele

002335

SKH2/J

View Strains carrying   mt-Tr^m2     (1 strain)

Strains carrying other alleles of Cdh23

002552	B6(V)-Cdh23v-2J/J
002756	B6.CAST-Cdh23Ahl+/Kjn
010615	B6.CBACa-Cdh23CBA/CaJ/Kjn
002432	B6J x B6.C-H2-Kbm1/ByJ-Cdh23v-J/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     (8 strains)

Strains carrying other alleles of mt-Tr

000646	A/J
003072	ALS/LtJ
001976	NOD/ShiLtJ
000684	NZB/BlNJ

View Strains carrying other alleles of mt-Tr     (4 strains)

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.

Phenotype

Phenotype Information

View Phenotypic Data

Phenotypic Data

Mouse Phenome Database

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Deafness, Autosomal Recessive 12; DFNB12   (CDH23) Usher Syndrome, Type ID; USH1D   (CDH23)

View Research Applications

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, Inflammation and Autoimmunity Research
Autoimmunity

Metabolism Research
Free Radical Research

Neurobiology Research
Hearing Defects
      Age related hearing loss

Research Tools
Toxicology Research
      free radical research

Sensorineural Research
Hearing Defects
      Age related hearing loss

Cdh23^ahl related

Neurobiology Research
Hearing Defects
      Age related hearing loss

Sensorineural Research
Hearing Defects
      Age related hearing loss

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cdh23ahl
Allele Name		age related hearing loss 1
Allele Type		QTL
Common Name(s)		Cdh23753A; mdfw;
Strain of Origin		multiple strains
Gene Symbol and Name		Cdh23, cadherin 23 (otocadherin)
Chromosome		10
Gene Common Name(s)		4930542A03Rik; CDHR23; 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; sals; salsa; 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, 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: C3H/HeSnJ, I/LnJ,YBR/Ei, MRL/MpJ. [MGI Ref ID J:86905]
Allele Symbol		mt-Trm2
Allele Name		mutation 2
Allele Type		Spontaneous
Common Name(s)		9A;
Strain of Origin		various
Gene Symbol and Name		mt-Tr, mitochondrially encoded tRNA arginine
Chromosome		MT
Gene Common Name(s)		TrnR tRNA; tRNA; tRNA-Arg;
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. [MGI Ref ID J:67312] [MGI Ref ID J:97969]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]  [MGI Ref ID 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]  [MGI Ref ID 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]  [MGI Ref ID 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]  [MGI Ref ID 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]  [MGI Ref ID J:57552]

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):902-11. [PubMed: 15081119]  [MGI Ref ID 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):269-72. [PubMed: 2361527]  [MGI Ref ID J:109930]

Additional References

Cdh23^ahl related

Bosco A; Crish SD; Steele MR; Romero CO; Inman DM; Horner PJ; Calkins DJ; Vetter ML. 2012. Early reduction of microglia activation by irradiation in a model of chronic glaucoma. PLoS One 7(8):e43602. [PubMed: 22952717]  [MGI Ref ID J:191663]

Davis RR; Newlander JK; Ling X; Cortopassi GA; Krieg EF; Erway LC. 2001. Genetic basis for susceptibility to noise-induced hearing loss in mice. Hear Res 155(1-2):82-90. [PubMed: 11335078]  [MGI Ref ID J:69679]

Di Palma F; Pellegrino R; Noben-Trauth K. 2001. Genomic structure, alternative splice forms and normal and mutant alleles of cadherin 23 (Cdh23). Gene 281(1-2):31-41. [PubMed: 11750125]  [MGI Ref ID J:73941]

Fetoni AR; Picciotti PM; Paludetti G; Troiani D. 2011. Pathogenesis of presbycusis in animal models: a review. Exp Gerontol 46(6):413-25. [PubMed: 21211561]  [MGI Ref ID J:186964]

Han F; Yu H; Tian C; Chen HE; Benedict-Alderfer C; Zheng Y; Wang Q; Han X; Zheng QY. 2010. A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs. Pharmacogenomics J :. [PubMed: 20644563]  [MGI Ref ID J:174758]

Johnson KR; Erway LC; Cook SA; Willott JF; Zheng QY. 1997. A major gene affecting age-related hearing loss in C57BL/6J mice Hear Res 114(1-2):83-92. [PubMed: 9447922]  [MGI Ref ID J:44966]

Johnson KR; Longo-Guess C; Gagnon LH; Yu H; Zheng QY. 2008. A locus on distal chromosome 11 (ahl8) and its interaction with Cdh23 ahl underlie the early onset, age-related hearing loss of DBA/2J mice. Genomics 92(4):219-25. [PubMed: 18662770]  [MGI Ref ID J:139223]

Johnson KR; Yu H; Ding D; Jiang H; Gagnon LH; Salvi RJ. 2010. Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice. Hear Res 268(1-2):85-92. [PubMed: 20470874]  [MGI Ref ID J:163035]

Johnson KR; Zheng QY; Bykhovskaya Y; Spirina O; Fischel-Ghodsian N. 2001. A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet 27(2):191-4. [PubMed: 11175788]  [MGI Ref ID J:67312]

Johnson KR; Zheng QY; Noben-Trauth K. 2006. Strain background effects and genetic modifiers of hearing in mice. Brain Res 1091(1):79-88. [PubMed: 16579977]  [MGI Ref ID J:110459]

Johnson KR; Zheng QY; Weston MD; Ptacek LJ; Noben-Trauth K. 2005. The Mass1(frings) mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics 85(5):582-90. [PubMed: 15820310]  [MGI Ref ID J:97534]

Kane KL; Longo-Guess CM; Gagnon LH; Ding D; Salvi RJ; Johnson KR. 2012. Genetic background effects on age-related hearing loss associated with Cdh23 variants in mice. Hear Res 283(1-2):80-8. [PubMed: 22138310]  [MGI Ref ID J:183757]

Keithley EM; Canto C; Zheng QY; Fischel-Ghodsian N; Johnson KR. 2004. Age-related hearing loss and the ahl locus in mice. Hear Res 188(1-2):21-8. [PubMed: 14759567]  [MGI Ref ID J:87783]

Liu X; Bulgakov OV; Darrow KN; Pawlyk B; Adamian M; Liberman MC; Li T. 2007. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci U S A 104(11):4413-8. [PubMed: 17360538]  [MGI Ref ID J:118927]

Manji SS; Williams LH; Miller KA; Ooms LM; Bahlo M; Mitchell CA; Dahl HH. 2011. A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart. PLoS One 6(3):e17607. [PubMed: 21423608]  [MGI Ref ID J:171701]

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]  [MGI Ref ID J:109893]

Nadeau JH. 2003. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13(3):290-5. [PubMed: 12787792]  [MGI Ref ID J:88012]

Noben-Trauth K; Latoche JR; Neely HR; Bennett B. 2010. Phenotype and genetics of progressive sensorineural hearing loss (Snhl1) in the LXS set of recombinant inbred strains of mice. PLoS One 5(7):e11459. [PubMed: 20628639]  [MGI Ref ID J:163117]

Noben-Trauth K; Zheng QY; Johnson KR. 2003. Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Nat Genet 35(1):21-3. [PubMed: 12910270]  [MGI Ref ID J:86905]

Noben-Trauth K; Zheng QY; Johnson KR; Nishina PM. 1997. mdfw: a deafness susceptibility locus that interacts with deaf waddler (dfw). Genomics 44(3):266-72. [PubMed: 9325047]  [MGI Ref ID J:38429]

Perrin BJ; Sonnemann KJ; Ervasti JM. 2010. beta-actin and gamma-actin are each dispensable for auditory hair cell development but required for Stereocilia maintenance. PLoS Genet 6(10):e1001158. [PubMed: 20976199]  [MGI Ref ID J:167543]

Vazquez AE; Jimenez AM; Martin GK; Luebke AE; Lonsbury-Martin BL. 2004. Evaluating cochlear function and the effects of noise exposure in the B6.CAST+Ahl mouse with distortion product otoacoustic emissions. Hear Res 194(1-2):87-96. [PubMed: 15276680]  [MGI Ref ID J:117746]

Zheng QY; Johnson KR. 2001. Hearing loss associated with the modifier of deaf waddler (mdfw) locus corresponds with age-related hearing loss in 12 inbred strains of mice. Hear Res 154(1-2):45-53. [PubMed: 11423214]  [MGI Ref ID J:70964]

Zheng QY; Scarborough JD; Zheng Y; Yu H; Choi D; Gillespie PG. 2012. Digenic inheritance of deafness caused by 8J allele of myosin-VIIA and mutations in other Usher I genes. Hum Mol Genet 21(11):2588-98. [PubMed: 22381527]  [MGI Ref ID J:183898]

Zilberstein Y; Liberman MC; Corfas G. 2012. Inner hair cells are not required for survival of spiral ganglion neurons in the adult cochlea. J Neurosci 32(2):405-10. [PubMed: 22238076]  [MGI Ref ID J:179911]

mt-Tr^m2 related

Johnson KR; Zheng QY; Bykhovskaya Y; Spirina O; Fischel-Ghodsian N. 2001. A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet 27(2):191-4. [PubMed: 11175788]  [MGI Ref ID J:67312]

Mathews CE; Leiter EH; Spirina O; Bykhovskaya Y; Gusdon AM; Ringquist S; Fischel-Ghodsian N. 2005. mt-Nd2 Allele of the ALR/Lt mouse confers resistance against both chemically induced and autoimmune diabetes. Diabetologia 48(2):261-7. [PubMed: 15692809]  [MGI Ref ID J:97969]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

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.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

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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