JAX Mouse Strain Datasheet - 001976

NOD/ShiLtJ

Stock No:: 001976 |; NOD

Inbred Strain

Readily Available

Overview

Also Known As: NOD, Non-obese Diabetic

The NOD/ShiLtJ strain (commonly called NOD) is a polygenic model for autoimmune type 1 diabetes. Diabetes in NOD mice is characterized by hyperglycemia and insulitis, a leukocytic infiltration of the pancreatic islets. Marked decreases in pancreatic insulin content occur in females at about 12 weeks of age and several weeks later in males. A 2017 phenotyping study found that 90% of females and 52% of males became diabetic by 30 weeks; median female incidence was 18 weeks. Immune phenotypes in the NOD background consist of defects in antigen presentation, T lymphocyte repertoire, NK cell function, macrophage cytokine production, wound healing, and C5 complement. These defects make the NOD background a common choice for immunodeficient mouse strains. Diabetes onset data is available.

Genetic overview

Genetic Background	Generation
	Contact Technical Support (27-JUL-18)

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Research Applications

Developmental Biology Research
Diabetes and Obesity Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Neurobiology Research
Research Tools
Sensorineural Research

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Base Price

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$34.40 Domestic price for male 3-week

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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 that is already severe by three months of age.

Detailed Description

Diabetes in NOD/ShiLtJ mice is characterized by insulitis, a leukocytic infiltrate of the pancreatic islets. Marked decreases in pancreatic insulin content occur in females at about 12 weeks of age and several weeks later in males. Onset of diabetes is marked by moderate glycosuria and by a non-fasting plasma glucose higher than 250 mg/dl. Diabetic mice are hypoinsulinemic and hyperglucagonemic, indicating a selective destruction of pancreatic islet beta cells. Susceptibility to IDDM in NOD/ShiLtJ mice is polygenic, and environment, including housing conditions, health status, and diet, exerts a strong effect on penetrance. NOD/ShiLtJ females are more widely used than males because the onset of IDDM symptoms occurs earlier and with a higher incidence (90-100% by 30 weeks of age). NOD/ShiLtJ males develop IDDM at a frequency of between 40-60% by 30-40 weeks of age. Male mice are useful for certain applications, including pharmaceutical studies, "accelerated transfer" of IDDM, and some in vitro studies. The major component of diabetes susceptibility in NOD mice is the unique MHC haplotype (H2^g7 = K^d, Aa^d, Ab^g7, E^null, D^b). NOD mice also exhibit multiple aberrant immunophenotypes including defective antigen presenting cell immunoregulatory functions, defects in the regulation of theT lymphocyte repertoire, defective NK cell function, defective cytokine production from macrophages (Fan et al., 2004) and impaired wound healing. They also lack hemolytic complement, C5. NOD/ShiLtJ mice also are severely hearing-impaired. A variety of mutations causing immunodeficiencies, targeted mutations in cytokine genes, as well as transgenes affecting immune functions, have been backcrossed into the NOD/ShiLt inbred strain background.

Development

NOD inbred mice originated early on in the inbreeding of the Cataract Shionogi (CTS) strain. These mice were originally outbred Jcl:ICR mice. At F6, the progenitors of the future NOD/Shi mice were inbred on the basis of an elevated fasting blood glucose level in cataract-free mice. At F13, the NOD progenitors were separated from what is now the NON/Shi strain. High fasting blood glucose levels continued to be the basis for selection of the latter strain, while the NOD progenitors at F13 and later were selected on the basis of a normal fasting blood glucose level. In 1974, at F20, a female in the "normoglycemic" line spontaneously developed overt insulin-dependent diabetes mellitus with insulitis (IDDM). Selective breeding of the progeny of this diabetic female produced the nonobese diabetic (NOD) strain. Originally restricted to distribution in Japan, NOD substrains were distributed during the early 1980s to Australia and the United States. NOD and NON strains were imported from a colony in Kyoto, Japan by Dr. M. Hattori to the Joslin Diabetes Ceneter in Boston in 1984. Breeder pairs from this importation were sent from The Joslin Diabetes Center to Dr. E Leiter at The Jackson Laboratory, and are the source of the production strains NOD/ShiLtJ and NON/ShiLtJ.

Control Suggestions

Approximate Controls

001303 NOD.CB17-Prkdc^scid/J, (May be used as an approximate control for T and B cell dependent research)
002050 NOR/LtJ, (Recombinant congenic that carries a portion of the NOD/ShiLtJ genome)
002591 NOD.B10Sn-H2^b/J
003729 NOD.129S7(B6)-Rag1^tm1Mom/J, (May be used as an approximate control for T and B cell dependent research)
009122 ICR/HaJ, (Both the inbred ICR/HaJ (Stock #009122) and NOD/ShiLtJ are descended from ICR stock. Testing at The Jackson Laboratory confirms that ICR/HaJ carries the H2^g7 MHC haplotype. ICR/HaJ does not develop insulitis or diabetes and may be considered an approximate control for NOD/ShiLtJ.)

Additional Information

Considerations for Choosing Controls

Selected References

Leiter EH. 1993. The NOD mouse: A model for analyzing the interplay between heredity and environment in development of autoimmune disease ILAR News 35(1):4-14. MGI: J:12784
Makino S; Kunimoto K; Muraoka Y; Mizushima Y; Katagiri K; Tochino Y. 1980. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu 29(1):1-13. PubMed: 6995140 MGI: J:25411
Serreze DV; Chapman HD; Varnum DS; Gerling I; Leiter EH; Shultz LD. 1997. Initiation of autoimmune diabetes in NOD/Lt mice is MHC class I-dependent. J Immunol 158(8):3978-86. PubMed: 9103469 MGI: J:39473
Simecek P; Churchill GA; Yang H; Rowe LB; Herberg L; Serreze DV; Leiter EH. 2015. Genetic Analysis of Substrain Divergence in Non-Obese Diabetic (NOD) Mice. G3 (Bethesda) 5(5):771-5. PubMed: 25740934 MGI: J:257336
Timmermans S; Van Montagu M; Libert C. 2017. Complete overview of protein-inactivating sequence variations in 36 sequenced mouse inbred strains. Proc Natl Acad Sci U S A 114(34):9158-9163. PubMed: 28784771 MGI: J:244295

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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)	4930542A03Rik; 4930542A03Rik; CDHR23; PITA5; RIKEN cDNA 4930542A03 gene; USH1D; W; age related hearing loss 1; ahl; ahl; bob; bob; bobby; bus; bustling; mdfw; mdfw; modifier of deaf waddler; neuroscience mutagenesis facility, 112; neuroscience mutagenesis facility, 181; neuroscience mutagenesis facility, 252; nmf112; nmf112; nmf181; nmf181; nmf252; nmf252; sals; sals; salsa; v; waltzer
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 nucleotide position 753 of Cdh23. This hypomorphic allele causes in frame skipping of exon 7, which 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: C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.

Del(1)2Lt

Allele Symbol: Del(1)2Lt

Allele Name	deletion, Chr 1, Edward H Leiter 2
Allele Type	Spontaneous (Not Applicable)
Allele Synonym(s)
Gene Symbol and Name	Del(1)2Lt, deletion, Chr 1, Edward H Leiter 2
Gene Synonym(s)	Del2Lt
Strain of Origin	NOD/ShiLtJ
Chromosome	1
Molecular Note	This spontaneous 25,703 bp deletion in Chromosome 1 spans from 39,088,990 bp to 39,114,692 bp (GRCm38).

Del(3)1Lt

Allele Symbol: Del(3)1Lt

Allele Name	deletion, Chr 3, Edward H Leiter 1
Allele Type	Spontaneous (Null/Knockout)
Allele Synonym(s)	Del1Lt
Gene Symbol and Name	Del(3)1Lt, deletion, Chr 3, Edward H Leiter 1
Gene Synonym(s)
Strain of Origin	NOD/ShiLtJ
Chromosome	3
Molecular Note	This spontaneous 111,169 bp deletion spans from Chr 3: 24,170,854 bp to 24,282,022 bp (GRCm38/mm10), and includes several QTL and the gene N-acetylated alpha-linked acidic dipeptidase-like 2

Del(3)3Lt

Allele Symbol: Del(3)3Lt

Allele Name	deletion, Chr 3, Edward H Leiter 3
Allele Type	Spontaneous (Not Applicable)
Allele Synonym(s)
Gene Symbol and Name	Del(3)3Lt, deletion, Chr 3, Edward H Leiter 3
Gene Synonym(s)	Del3Lt
Strain of Origin	NOD/ShiLtJ
Chromosome	3
Molecular Note	This spontaneous 4,289 bp deletion in Chromosome 3 spans from 33,746,227 bp to 33,750,515 bp (GRCm38).

Gpr84^del

Allele Symbol: Gpr84^del

Allele Name	deletion
Allele Type	Spontaneous (Not Specified)
Allele Synonym(s)
Gene Symbol and Name	Gpr84, G protein-coupled receptor 84
Gene Synonym(s)	EX33; GPCR4
Strain of Origin	multiple strains
Chromosome	15
Molecular Note	This spontaneously arising frameshift deletion is located in exon 2 at position 103308576 bp (NCBI Build 37) and results in a premature stop codon. The mutation is predicted to result in a truncated protein lacking the transmembrane domains 4-7. The inbred strains BDP/J, DBA/1J, DBA/2J, I/LnJ, FVB/NJ, LG/J, MRL/MpJ, NODShi/LtJ, NOR/LtJ, P/J, PL/J, SKHIN/Sprd, SJL/J, SM/J are homozygous for the deletion. The allele is segregating in the outbred stocks ICR and CD-1.

H2^g7

Allele Symbol: H2^g7

Allele Name	g7 variant
Allele Type	Not Applicable
Allele Synonym(s)	H-2^g7; H-2g7
Gene Symbol and Name	H2, histocompatibility-2, MHC
Gene Synonym(s)	H-2; H-2; MHC-II
Strain of Origin	Not Applicable
Chromosome	17
General Note	The g7 variant has been observed in the following strains: DBR7, NON.NOD-H2^g7

Hc⁰

Allele Symbol: Hc⁰

Allele Name	deficient
Allele Type	Spontaneous
Allele Synonym(s)	C5-; C5-d; C5-def; C5-deficient; Hc^Hfib2; hc^o
Gene Symbol and Name	Hc, hemolytic complement
Gene Synonym(s)	C5; C5; C5D; C5a; C5b; CPAMD4; ECLZB; He; He; Hfib2; Hfib2; hepatic fibrogenesis 2
Strain of Origin	multiple strains
Chromosome	2
General Note	This is an allele characteristic of various inbred mouse strains including the following: A/HeJ, A/J, AKR/J, DBA/2J, NZB/B1NJ, SWR/J, B10.D2/oSnJ Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The A/J allele contains a 2 bp deletion resulting in deficient Hc mRNA and protein production and is associated with susceptibility to allergen-induced bronchial hyperresponsiveness. (J:108211)
Molecular Note	A 2 base "TA" deletion at positions 62 and 63 of an 83 base pair exon near the 5' end of the gene is found in the following mouse strains: A/HeJ, A/J, AKR/J, DBA/2J, I/LnJ, KK/HlJ, MOLF/EiJ, NZB/B1NJ, RF/J, ST/bJ SWR/J, B10.D2/oSnJ. The consequence of this deletion is the creation of a stop codon starting four bases after the deletion. A truncated product of 216 amino acids is predicted as a result although contradictory reports exist that a larger pro-C5 protein may be synthesized. Nevertheless, macrophages from mouse strains carrying this allele do not secrete complement 5.

Il2^m1

Allele Symbol: Il2^m1

Allele Name	mutation 1
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Il2, interleukin 2
Gene Synonym(s)	IL-2; Il-2; TCGF; lymphokine
Strain of Origin	multiple strains
Chromosome	3
Molecular Note	This hypoactive polymorphism, found in MRL/MpJ, SJL/J, and NOD/ShiLtJ inbred strains, includes a smaller polyglutamine tract predicted to shorten the first alpha helix, which forms part of the IL2 receptor binding site.

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)	MTTR; TrnR tRNA; tRNA; tRNA-Arg
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

Research Areas By Genotype

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

Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects
Diabetes and Obesity Research
- Hyperglycemia
- Hypoinsulinemia
- Impaired Wound Healing
- Islet Transplantation Studies
- Type 1 Diabetes (IDDM)
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - Type 1 Diabetes
Internal/Organ Research
- Wound Healing
  - delayed/impaired
Neurobiology Research
- Hearing Defects
  - Age related hearing loss
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - NK Cell Deficiency
Sensorineural Research
- Hearing Defects
  - Age related hearing loss

Genotype: Cdh23^ahl related

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

Genotype: H2^g7 related

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genotype: Hc⁰ related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - specific complement deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - specific complement deficiency, C5 complement

Phenotype Information

Body Weight Information - JAX^® Mice Strain NOD/ShiLtJ (001976)

References

Leiter EH. 1993. The NOD mouse: A model for analyzing the interplay between heredity and environment in development of autoimmune disease ILAR News 35(1):4-14. MGI: J:12784
Makino S; Kunimoto K; Muraoka Y; Mizushima Y; Katagiri K; Tochino Y. 1980. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu 29(1):1-13. PubMed: 6995140 MGI: J:25411
Serreze DV; Chapman HD; Varnum DS; Gerling I; Leiter EH; Shultz LD. 1997. Initiation of autoimmune diabetes in NOD/Lt mice is MHC class I-dependent. J Immunol 158(8):3978-86. PubMed: 9103469 MGI: J:39473
Simecek P; Churchill GA; Yang H; Rowe LB; Herberg L; Serreze DV; Leiter EH. 2015. Genetic Analysis of Substrain Divergence in Non-Obese Diabetic (NOD) Mice. G3 (Bethesda) 5(5):771-5. PubMed: 25740934 MGI: J:257336
Timmermans S; Van Montagu M; Libert C. 2017. Complete overview of protein-inactivating sequence variations in 36 sequenced mouse inbred strains. Proc Natl Acad Sci U S A 114(34):9158-9163. PubMed: 28784771 MGI: J:244295

Additional References

Bowman MA; Leiter EH; Atkinson MA. 1994. Prevention of diabetes in the NOD mouse: implications for therapeutic intervention in human disease. Immunol Today 15(3):115-20. PubMed: 8172643 MGI: J:17091
Chun T; Hermel E; Gaskins HR; Aldrich CJ. 2001. Cytotoxic T lymphocyte and cDNA sequence analyses of the MHC class Ib molecule Qa1 in nonobese diabetic mice. Immunogenetics 53(6):506-10. PubMed: 11685462 MGI: J:72438
Darby IA; Bisucci T; Hewitson TD; MacLellan DG. 1997. Apoptosis is increased in a model of diabetes-impaired wound healing in genetically diabetic mice. Int J Biochem Cell Biol 29(1):191-200. PubMed: 9076954 MGI: J:40898
Depis F; Kwon HK; Mathis D; Benoist C. 2016. Unstable FoxP3+ T regulatory cells in NZW mice. Proc Natl Acad Sci U S A 113(5):1345-50. PubMed: 26768846 MGI: J:227903
DiLorenzo TP; Lieberman SM; Takaki T; Honda S; Chapman HD; Santamaria P; Serreze DV; Nathenson SG. 2002. During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities. Clin Immunol 105(3):332-41. PubMed: 12498815 MGI: J:94192
Hui ST; Parks BW; Org E; Norheim F; Che N; Pan C; Castellani LW; Charugundla S; Dirks DL; Psychogios N; Neuhaus I; Gerszten RE; Kirchgessner T; Gargalovic PS; Lusis AJ. 2015. The genetic architecture of NAFLD among inbred strains of mice. Elife 4:e05607. PubMed: 26067236 MGI: J:223755
Keane TM; Goodstadt L; Danecek P; White MA; Wong K; Yalcin B; Heger A; Agam A; Slater G; Goodson M; Furlotte NA; Eskin E; Nellaker C; Whitley H; Cleak J; Janowitz D; Hernandez-Pliego P; Edwards A; Belgard TG; Oliver PL; McIntyre RE; Bhomra A; Nicod J; Gan X; Yuan W; van der Weyden L; Steward CA; Bala S; Stalker J; Mott R; Durbin R; Jackson IJ; Czechanski A; Guerra-Assuncao JA; Donahue LR; Reinholdt LG; Payseur BA; Ponting CP; Birney E; Flint J; Adams DJ. 2011. Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477(7364):289-94. PubMed: 21921910 MGI: J:177037
Leiter EH. 1998. NOD Mice and Related Strains: Origins, Husbandry and Biology Introduction. In: NOD Mice and Related Strains: Research Applications in Diabetes, AIDS, Cancer, and Other Diseases. RG Landes, Austin. MGI: J:110093
Lynch DM; Kay PH. 1995. Studies on the polymorphism of the fifth component of complement in laboratory mice. Exp Clin Immunogenet 12(4):253-60. PubMed: 8919358 MGI: J:31912
Moy SS; Nadler JJ; Young NB; Nonneman RJ; Segall SK; Andrade GM; Crawley JN; Magnuson TR. 2008. Social approach and repetitive behavior in eleven inbred mouse strains. Behav Brain Res 191(1):118-29. PubMed: 18440079 MGI: J:138681
Nagy A; Nagashima H; Cha S; Oxford GE; Zelles T; Peck AB; Humphreys-Beher MG. 2001. Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes and its reversal by epidermal growth factor supplementation. Diabetes 50(9):2100-4. PubMed: 11522677 MGI: J:71049
Nutter CA; Jaworski EA; Verma SK; Deshmukh V; Wang Q; Botvinnik OB; Lozano MJ; Abass IJ; Ijaz T; Brasier AR; Garg NJ; Wehrens XH; Yeo GW; Kuyumcu-Martinez MN. 2016. Dysregulation of RBFOX2 Is an Early Event in Cardiac Pathogenesis of Diabetes. Cell Rep 15(10):2200-13. PubMed: 27239029 MGI: J:238102
Odet F; Pan W; Bell TA; Goodson SG; Stevans AM; Yun Z; Aylor DL; Kao CY; McMillan L; de Villena FP; O'Brien DA. 2015. The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction. G3 (Bethesda) 5(12):2671-83. PubMed: 26483008 MGI: J:244582
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: J:89298
Pierce MA; Chapman HD; Post CM; Svetlanov A; Efrat S; Horwitz M; Serreze DV. 2003. Adenovirus early region 3 antiapoptotic 10.4K, 14.5K, and 14.7K genes decrease the incidence of autoimmune diabetes in NOD mice. Diabetes 52(5):1119-27. PubMed: 12716741 MGI: J:83195
Quintana FJ; Cohen IR. 2001. Autoantibody Patterns in Diabetes-prone NOD Mice and in Standard C57BL/6 Mice. J Autoimmun 17(3):191-7. PubMed: 11712856 MGI: J:72893
Serr I; Scherm MG; Zahm AM; Schug J; Flynn VK; Hippich M; Kalin S; Becker M; Achenbach P; Nikolaev A; Gerlach K; Liebsch N; Loretz B; Lehr CM; Kirchner B; Spornraft M; Haase B; Segars J; Kuper C; Palmisano R; Waisman A; Willis RA; Kim WU; Weigmann B; Kaestner KH; Ziegler AG; Daniel C. 2018. A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes. Sci Transl Med 10(422):. PubMed: 29298866 MGI: J:254437
Serreze DV; Leiter EH. 1994. Genetic and pathogenic basis of autoimmune diabetes in NOD mice. Curr Opin Immunol 6(6):900-6. PubMed: 7710714 MGI: J:22216
Serreze DV; Post CM; Chapman HD; Johnson EA; Lu B; Rothman PB. 2000. Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice. Diabetes 49(12):2007-11. PubMed: 11118001 MGI: J:65986
Trembleau S; Gregori S; Penna G; Gorny I; Adorini L. 2001. Il-12 administration reveals diabetogenic t cells in genetically resistant i-ealpha-transgenic nonobese diabetic mice: resistance to autoimmune diabetes is associated with binding of ealpha-derived peptides to the i-a(g7) molecule. J Immunol 167(7):4104-14. PubMed: 11564833 MGI: J:71651
Xie C; Sharma R; Wang H; Zhou XJ; Mohan C. 2004. Strain distribution pattern of susceptibility to immune-mediated nephritis. J Immunol 172(8):5047-55. PubMed: 15067087 MGI: J:122988

Additional - 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: 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: 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: 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: J:186964
Han F; Yu H; Tian C; Chen HE; Benedict-Alderfer C; Zheng Y; Wang Q; Han X; Zheng QY. 2012. A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs. Pharmacogenomics J 12(1):30-44. PubMed: 20644563 MGI: J:174758
Hurd EA; Adams ME; Layman WS; Swiderski DL; Beyer LA; Halsey KE; Benson JM; Gong TW; Dolan DF; Raphael Y; Martin DM. 2011. Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome. Hear Res 282(1-2):184-95. PubMed: 21875659 MGI: J:220430
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: 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: J:139223
Johnson KR; Tian C; Gagnon LH; Jiang H; Ding D; Salvi R. 2017. Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL/6 and 129S1/Sv mice and comparisons with congenic strains. Sci Rep 7:44450. PubMed: 28287619 MGI: J:241137
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: 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: 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: 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: 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: 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: 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: 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: 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: J:109893
Miyasaka Y; Suzuki S; Ohshiba Y; Watanabe K; Sagara Y; Yasuda SP; Matsuoka K; Shitara H; Yonekawa H; Kominami R; Kikkawa Y. 2013. Compound heterozygosity of the functionally null Cdh23(v-ngt) and hypomorphic Cdh23(ahl) alleles leads to early-onset progressive hearing loss in mice. Exp Anim 62(4):333-46. PubMed: 24172198 MGI: J:250509
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Additional - Gpr84^del related

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Additional - H2^g7 related

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Additional - Hc⁰ related

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Kwan WH; Hashimoto D; Paz-Artal E; Ostrow K; Greter M; Raedler H; Medof ME; Merad M; Heeger PS. 2012. Antigen-presenting cell-derived complement modulates graft-versus-host disease. J Clin Invest 122(6):2234-8. PubMed: 22585573 MGI: J:190492
Kyriakides C; Austen W Jr; Wang Y; Favuzza J; Kobzik L; Moore FD Jr; Hechtman HB. 1999. Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration. J Appl Physiol 87(6):2357-61. PubMed: 10601189 MGI: J:103341
Lee HM; Wu W; Wysoczynski M; Liu R; Zuba-Surma EK; Kucia M; Ratajczak J; Ratajczak MZ. 2009. Impaired mobilization of hematopoietic stem/progenitor cells in C5-deficient mice supports the pivotal involvement of innate immunity in this process and reveals novel promobilization effects of granulocytes. Leukemia 23(11):2052-62. PubMed: 19657368 MGI: J:154482
Lee HM; Wysoczynski M; Liu R; Shin DM; Kucia M; Botto M; Ratajczak J; Ratajczak MZ. 2010. Mobilization studies in complement-deficient mice reveal that optimal AMD3100 mobilization of hematopoietic stem cells depends on complement cascade activation by AMD3100-stimulated granulocytes. Leukemia 24(3):573-82. PubMed: 20033053 MGI: J:158026
Liu Q; He S; Groysman L; Shaked D; Russin J; Cen S; Mack WJ. 2013. White matter injury due to experimental chronic cerebral hypoperfusion is associated with C5 deposition. PLoS One 8(12):e84802. PubMed: 24386419 MGI: J:209840
Mahesh J; Daly J; Cheadle WG; Kotwal GJ. 1999. Elucidation of the early events contributing to zymosan-induced multiple organ dysfunction syndrome using MIP-1alpha, C3 knockout, and C5-deficient mice. Shock 12(5):340-9. PubMed: 10565608 MGI: J:59655
Mastellos D; Papadimitriou JC; Franchini S; Tsonis PA; Lambris JD. 2001. A novel role of complement: mice deficient in the fifth component of complement (C5) exhibit impaired liver regeneration. J Immunol 166(4):2479-86. PubMed: 11160308 MGI: J:111000
Miller CG; Cook DN; Kotwal GJ. 1996. Two chemotactic factors, C5a and MIP-1alpha, dramatically alter the mortality from zymosan-induced multiple organ dysfunction syndrome (MODS): C5a contributes to MODS while MIP-1alpha has a protective role. Mol Immunol 33(14):1135-7. PubMed: 9047380 MGI: J:38592
Miller CG; Justus DE; Jayaraman S; Kotwal GJ. 1995. Severe and prolonged inflammatory response to localized cowpox virus infection in footpads of C5-deficient mice: investigation of the role of host complement in poxvirus pathogenesis. Cell Immunol 162(2):326-32. PubMed: 7743560 MGI: J:25289
Miwa T; Zhou L; Kimura Y; Kim D; Bhandoola A; Song WC. 2009. Complement-dependent T-cell lymphopenia caused by thymocyte deletion of the membrane complement regulator Crry. Blood 113(12):2684-94. PubMed: 19136662 MGI: J:146538
Mocco J; Mack WJ; Ducruet AF; Sosunov SA; Sughrue ME; Hassid BG; Nair MN; Laufer I; Komotar RJ; Claire M; Holland H; Pinsky DJ; Connolly ES Jr. 2006. Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res 99(2):209-17. PubMed: 16778128 MGI: J:123658
Mori L; de Libero G. 1998. Genetic control of susceptibility to collagen-induced arthritis in T cell receptor beta-chain transgenic mice. Arthritis Rheum 41(2):256-62. PubMed: 9485083 MGI: J:134111
Moulton RA; Mashruwala MA; Smith AK; Lindsey DR; Wetsel RA; Haviland DL; Hunter RL; Jagannath C. 2007. Complement C5a anaphylatoxin is an innate determinant of dendritic cell-induced Th1 immunity to Mycobacterium bovis BCG infection in mice. J Leukoc Biol 82(4):956-67. PubMed: 17675563 MGI: J:125190
Mullick A; Elias M; Picard S; Bourget L; Jovcevski O; Gauthier S; Tuite A; Harakidas P; Bihun C; Massie B; Gros P. 2004. Dysregulated inflammatory response to Candida albicans in a C5-deficient mouse strain. Infect Immun 72(10):5868-76. PubMed: 15385488 MGI: J:93132
Mullick A; Leon Z; Min-Oo G; Berghout J; Lo R; Daniels E; Gros P. 2006. Cardiac failure in C5-deficient A/J mice after Candida albicans infection. Infect Immun 74(8):4439-51. PubMed: 16861630 MGI: J:112405
Niculescu T; Weerth S; Niculescu F; Cudrici C; Rus V; Raine CS; Shin ML; Rus H. 2004. Effects of complement C5 on apoptosis in experimental autoimmune encephalomyelitis. J Immunol 172(9):5702-6. PubMed: 15100315 MGI: J:89686
Nilsson UR; Muller-Eberhard HJ. 1967. Deficiency of the fifth component of complement in mice with an inherited complement defect. J Exp Med 125(1):1-16. PubMed: 4959665 MGI: J:5016
Ooi YM; Colten HR. 1979. Genetic defect in secretion of complement C5 in mice. Nature 282(5735):207-8. PubMed: 492335 MGI: J:6214
Patel SN; Berghout J; Lovegrove FE; Ayi K; Conroy A; Serghides L; Min-oo G; Gowda DC; Sarma JV; Rittirsch D; Ward PA; Liles WC; Gros P; Kain KC. 2008. C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. J Exp Med 205(5):1133-43. PubMed: 18426986 MGI: J:136298
Pickering MC; Warren J; Rose KL; Carlucci F; Wang Y; Walport MJ; Cook HT; Botto M. 2006. Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice. Proc Natl Acad Sci U S A 103(25):9649-54. PubMed: 16769899 MGI: J:111031
Pilione MR; Agosto LM; Kennett MJ; Harvill ET. 2006. CD11b is required for the resolution of inflammation induced by Bordetella bronchiseptica respiratory infection. Cell Microbiol 8(5):758-68. PubMed: 16611225 MGI: J:135740
Pritchard MT; McMullen MR; Stavitsky AB; Cohen JI; Lin F; Medof ME; Nagy LE. 2007. Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice. Gastroenterology 132(3):1117-26. PubMed: 17383432 MGI: J:128218
Prodeus AP; Zhou X; Maurer M; Galli SJ; Carroll MC. 1997. Impaired mast cell-dependent natural immunity in complement C3-deficient mice. Nature 390(6656):172-5. PubMed: 9367154 MGI: J:44240
Ratajczak MZ; Lee H; Wysoczynski M; Wan W; Marlicz W; Laughlin MJ; Kucia M; Janowska-Wieczorek A; Ratajczak J. 2010. Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due toactivation of complement cascade/membrane attack complex. Leukemia 24(5):976-85. PubMed: 20357827 MGI: J:160183
Redecha P; Tilley R; Tencati M; Salmon JE; Kirchhofer D; Mackman N; Girardi G. 2007. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood 110(7):2423-31. PubMed: 17536017 MGI: J:147022
Refici ML; Metzger DW; Arulanandam BP; Lennartz MR; Loegering DJ. 2001. Fcgamma-receptor signaling augments the LPS-stimulated increase in serum tumor necrosis factor-alpha levels. Am J Physiol Regul Integr Comp Physiol 280(4):R1037-44. PubMed: 11247825 MGI: J:114295
Rittirsch D; Flierl MA; Day DE; Nadeau BA; McGuire SR; Hoesel LM; Ipaktchi K; Zetoune FS; Sarma JV; Leng L; Huber-Lang MS; Neff TA; Bucala R; Ward PA. 2008. Acute lung injury induced by lipopolysaccharide is independent of complement activation. J Immunol 180(11):7664-72. PubMed: 18490769 MGI: J:136379
Rittirsch D; Flierl MA; Nadeau BA; Day DE; Huber-Lang M; Mackay CR; Zetoune FS; Gerard NP; Cianflone K; Kohl J; Gerard C; Sarma JV; Ward PA. 2008. Functional roles for C5a receptors in sepsis. Nat Med 14(5):551-7. PubMed: 18454156 MGI: J:136703
Saville SP; Lazzell AL; Chaturvedi AK; Monteagudo C; Lopez-Ribot JL. 2008. Use of a genetically engineered strain to evaluate the pathogenic potential of yeast cell and filamentous forms during Candida albicans systemic infection in immunodeficient mice. Infect Immun 76(1):97-102. PubMed: 17967861 MGI: J:130296
Schmitt J; Roderfeld M; Sabrane K; Zhang P; Tian Y; Mertens JC; Frei P; Stieger B; Weber A; Mullhaupt B; Roeb E; Geier A. 2012. Complement factor C5 deficiency significantly delays the progression of biliary fibrosis in bile duct-ligated mice. Biochem Biophys Res Commun 418(3):445-50. PubMed: 22277671 MGI: J:181268
Schultz G; Tedesco MM; Sho E; Nishimura T; Sharif S; Du X; Myles T; Morser J; Dalman RL; Leung LL. 2010. Enhanced abdominal aortic aneurysm formation in thrombin-activatable procarboxypeptidase B-deficient mice. Arterioscler Thromb Vasc Biol 30(7):1363-70. PubMed: 20431069 MGI: J:180861
Sood R; Sholl L; Isermann B; Zogg M; Coughlin SR; Weiler H. 2008. Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin. Blood 112(3):585-91. PubMed: 18490515 MGI: J:138440
Stokol T; O'Donnell P; Xiao L; Knight S; Stavrakis G; Botto M; von Andrian UH; Mayadas TN. 2004. C1q governs deposition of circulating immune complexes and leukocyte Fcgamma receptors mediate subsequent neutrophil recruitment. J Exp Med 200(7):835-46. PubMed: 15466618 MGI: J:93949
Strainic MG; Liu J; Huang D; An F; Lalli PN; Muqim N; Shapiro VS; Dubyak GR; Heeger PS; Medof ME. 2008. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 28(3):425-35. PubMed: 18328742 MGI: J:132942
Strainic MG; Shevach EM; An F; Lin F; Medof ME. 2012. Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta1 signaling and induction of Foxp3(+) regulatory T cells. Nat Immunol 14(2):162-71. PubMed: 23263555 MGI: J:192613
Strey CW; Markiewski M; Mastellos D; Tudoran R; Spruce LA; Greenbaum LE; Lambris JD. 2003. The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med 198(6):913-23. PubMed: 12975457 MGI: J:109380
Syed SN; Rau E; Ziegelmann M; Sogkas G; Brune B; Schmidt RE. 2018. C5aR activation in the absence of C5a: A new disease mechanism of autoimmune hemolytic anemia in mice. Eur J Immunol 48(4):696-704. PubMed: 29277896 MGI: J:261609
Tanaka D; Kagari T; Doi H; Shimozato T. 2006. Essential role of neutrophils in anti-type II collagen antibody and lipopolysaccharide-induced arthritis. Immunology 119(2):195-202. PubMed: 16836650 MGI: J:118551
Trendelenburg M; Fossati-Jimack L; Cortes-Hernandez J; Turnberg D; Lewis M; Izui S; Cook HT; Botto M. 2005. The role of complement in cryoglobulin-induced immune complex glomerulonephritis. J Immunol 175(10):6909-14. PubMed: 16272350 MGI: J:119691
Wang Y; Kristan J; Hao L; Lenkoski CS; Shen Y; Matis LA. 2000. A role for complement in antibody-mediated inflammation: C5-deficient DBA/1 mice are resistant to collagen-induced arthritis. J Immunol 164(8):4340-7. PubMed: 10754334 MGI: J:61587
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Additional - Il2^m1 related

Choi Y; Simon-Stoos K; Puck J. 2002. Hypo-active variant of IL-2 and associated decreased T cell activation contribute to impaired apoptosis in autoimmune prone MRL mice. Eur J Immunol 32(3):677-85. PubMed: 11857342 MGI: J:75331

Additional - mt-Tr^m1 related

Johnson KR; Gagnon LH; Longo-Guess C; Kane KL. 2012. Association of a citrate synthase missense mutation with age-related hearing loss in A/J mice. Neurobiol Aging 33(8):1720-9. PubMed: 21803452 MGI: J:188196
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: 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: J:110459
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: J:97969

Also Known As: NOD, Non-obese Diabetic

Genetic overview

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Cdh23ahl

Allele Symbol: Cdh23ahl

Del(1)2Lt

Allele Symbol: Del(1)2Lt

Del(3)1Lt

Allele Symbol: Del(3)1Lt

Del(3)3Lt

Allele Symbol: Del(3)3Lt

Gpr84del

Allele Symbol: Gpr84del

H2g7

Allele Symbol: H2g7

Hc0

Allele Symbol: Hc0

Il2m1

Allele Symbol: Il2m1

mt-Trm1

Allele Symbol: mt-Trm1

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

Genotype: Cdh23ahl related

Genotype: H2g7 related

Genotype: Hc0 related

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Additional - Cdh23ahl related

Additional - Gpr84del related

Additional - H2g7 related

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Additional - Il2m1 related

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Cdh23^ahl

Allele Symbol: Cdh23^ahl

Gpr84^del

Allele Symbol: Gpr84^del

H2^g7

Allele Symbol: H2^g7

Hc⁰

Allele Symbol: Hc⁰

Il2^m1

Allele Symbol: Il2^m1

mt-Tr^m1

Allele Symbol: mt-Tr^m1

Genotype: Cdh23^ahl related

Genotype: H2^g7 related

Genotype: Hc⁰ related

Additional - Cdh23^ahl related

Additional - Gpr84^del related

Additional - H2^g7 related

Additional - Hc⁰ related

Additional - Il2^m1 related

Additional - mt-Tr^m1 related