JAX
Mouse Strain Datasheet - 007048
DBA/2J-Gpnmb+/SjJ
This coisogenic strain has a functional allele of Gpnmb. Homozygous mice do not develop the elevated intraocular pressure or glaucoma found in DBA/2J mice (Stock 000671), although they exhibit a mild iris stromal atrophy (ISA). This strain provides a genetically matched control for DBA/2J.
Read More +Research Applications
- Sensorineural Research
- Neurobiology Research
- Immunology, Inflammation and Autoimmunity Research
- Research Tools
Important Note
This strain is homozygous for Cdh23ahl, 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
This coisogenic strain has a functional allele of Gpnmb. Homozygous mice do not develop elevated intraocular pressure or glaucoma, although they exhibit a mild iris stromal atrophy (ISA). This strain provides a genetically matched control for DBA/2J (Stock No. 000671). The inbred strain DBA/2J is homozygous for the glaucoma-related GpnmbR150X and Tyrp1isa mutations.
Development
The wildtype allele of Gpnmb is present in the mutant strain DBA/2J-Dtnbp1sdy/J. The sandy mutation occurred in 1983 prior to the appearance of the GpnmbR150X mutation in the The Jackson Laboratory DBA/2J production colony. To generate this strain, mice from DBA/2J-Dtnbp1sdy/J were crossed to "modern" DBA/2J mice, and progeny were selected for the Gpnmb wildtype allele. The wildtype allele was backcrossed to DBA/2J for a minimum of six generations. Dr. Simon John of The Jackson Laboratory provided the colony to the Repository in 2007.
Control Suggestions
Selected References
- Howell GR; Libby RT; Marchant JK; Wilson LA; Cosma IM; Smith RS; Anderson MG; John SW. 2007. Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1. BMC Genet 8(1):45. PubMed: 17608931MGI: J:123136
Cdh23ahl
Allele Symbol: Cdh23ahl
| Allele Name | age related hearing loss 1 |
|---|---|
| Allele Type | Spontaneous |
| Allele Synonym(s) | Cdh23753A; mdfw |
| Gene Symbol and Name | Cdh23, cadherin 23 (otocadherin) |
| Gene Synonym(s) | 4930542A03Rik; 4930542A03Rik; CDHR23; 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: 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. |
Gpnmb+
Allele Symbol: Gpnmb+
| Allele Name | wild type |
|---|---|
| Allele Type | Not Applicable |
| Allele Synonym(s) | |
| Gene Symbol and Name | Gpnmb, glycoprotein (transmembrane) nmb |
| Gene Synonym(s) | DC-HIL; Dchil; Dchil; HGFIN; NMB; Osteoactivin; dendritic cell associated heparan sulfate proteoglycans dependent integrin ligand; ipd; iris pigment dispersion |
| Site of Expression | Iris of the eys. |
| Strain of Origin | Not Applicable |
| Chromosome | 6 |
Hc0
Allele Symbol: Hc0
| Allele Name | deficient |
|---|---|
| Allele Type | Spontaneous |
| Allele Synonym(s) | C5-; C5-d; C5-def; C5-deficient; hco |
| Gene Symbol and Name | Hc, hemolytic complement |
| Gene Synonym(s) | C5; C5; C5D; C5a; C5b; CPAMD4; ECLZB; He; He |
| Strain of Origin | multiple strains |
| Chromosome | 2 |
| General Note | This is an allele characteristic of various inbred mouse strains including the following: A/HeJ, 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, AKR/J, DBA/2J, NZB/B1NJ, 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. |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Sensorineural Research
- Eye Defects
- control
- Eye Defects
Genotype: Cdh23ahl related
- Neurobiology Research
- Hearing Defects
- Age related hearing loss
- Hearing Defects
- Sensorineural Research
- Hearing Defects
- Age related hearing loss
- Hearing Defects
Genotype: Hc0 related
- Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
- specific complement deficiency
- Immunodeficiency
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- specific complement deficiency, C5 complement
- Immunology, Inflammation and Autoimmunity Research
References
- Howell GR; Libby RT; Marchant JK; Wilson LA; Cosma IM; Smith RS; Anderson MG; John SW. 2007. Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1. BMC Genet 8(1):45. PubMed: 17608931MGI: J:123136
Additional References
- Howell GR; Libby RT; Jakobs TC; Smith RS; Phalan FC; Barter JW; Barbay JM; Marchant JK; Mahesh N; Porciatti V; Whitmore AV; Masland RH; John SW. 2007. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J Cell Biol 179(7):1523-37. PubMed: 18158332MGI: J:131073
Additional - Cdh23ahl 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: 22952717MGI: 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: 11335078MGI: 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: 11750125MGI: 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: 21211561MGI: 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: 20644563MGI: 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: 21875659MGI: 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: 9447922MGI: 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: 18662770MGI: 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: 28287619MGI: 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: 20470874MGI: 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: 11175788MGI: 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: 16579977MGI: 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: 15820310MGI: 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: 22138310MGI: 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: 14759567MGI: 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: 17360538MGI: 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: 21423608MGI: 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: 10535453MGI: J:109893
- Murillo-Cuesta S; Rodriguez-de la Rosa L; Contreras J; Celaya AM; Camarero G; Rivera T; Varela-Nieto I. 2015. Transforming growth factor beta1 inhibition protects from noise-induced hearing loss. Front Aging Neurosci 7:32. PubMed: 25852546MGI: J:242536
- Nadeau JH. 2003. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13(3):290-5. PubMed: 12787792MGI: J:88012
- Nagtegaal AP; Rainey RN; van der Pluijm I; Brandt RM; van der Horst GT; Borst JG; Segil N. 2015. Cockayne syndrome group B (csb) and group a (csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice. J Neurosci 35(10):4280-6. PubMed: 25762674MGI: J:219993
- 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: 20628639MGI: 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: 12910270MGI: 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: 9325047MGI: 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: 20976199MGI: J:167543
- Perrin BJ; Strandjord DM; Narayanan P; Henderson DM; Johnson KR; Ervasti JM. 2013. beta-Actin and Fascin-2 Cooperate to Maintain Stereocilia Length. J Neurosci 33(19):8114-21. PubMed: 23658152MGI: J:197137
- 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: 15276680MGI: J:117746
- Watson CJ; Tempel BL. 2013. A new Atp2b2 deafwaddler allele, dfw(i5), interacts strongly with Cdh23 and other auditory modifiers. Hear Res 304:41-8. PubMed: 23792079MGI: J:220660
- 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: 11423214MGI: 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: 22381527MGI: 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: 22238076MGI: J:179911
Additional - Gpnmb+ 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: 22952717MGI: J:191663
- Howell GR; Libby RT; Jakobs TC; Smith RS; Phalan FC; Barter JW; Barbay JM; Marchant JK; Mahesh N; Porciatti V; Whitmore AV; Masland RH; John SW. 2007. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J Cell Biol 179(7):1523-37. PubMed: 18158332MGI: J:131073
- Huang W; Xing W; Ryskamp DA; Punzo C; Krizaj D. 2011. Localization and phenotype-specific expression of ryanodine calcium release channels in C57BL6 and DBA/2J mouse strains. Exp Eye Res 93(5):700-9. PubMed: 21933672MGI: J:189480
- Nguyen JV; Soto I; Kim KY; Bushong EA; Oglesby E; Valiente-Soriano FJ; Yang Z; Davis CH; Bedont JL; Son JL; Wei JO; Buchman VL; Zack DJ; Vidal-Sanz M; Ellisman MH; Marsh-Armstrong N. 2011. Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma. Proc Natl Acad Sci U S A 108(3):1176-81. PubMed: 21199938MGI: J:168848
- Porciatti V; Chou TH; Feuer WJ. 2010. C57BL/6J, DBA/2J, and DBA/2J.Gpnmb mice have different visual signal processing in the inner retina. Mol Vis 16:2939-47. PubMed: 21203347MGI: J:168340
- Williams PA; Howell GR; Barbay JM; Braine CE; Sousa GL; John SW; Morgan JE. 2013. Retinal ganglion cell dendritic atrophy in DBA/2J glaucoma. PLoS One 8(8):e72282. PubMed: 23977271MGI: J:199858
Additional - Hc0 related
- Actor JK; Breij E; Wetsel RA; Hoffmann H; Hunter RL Jr; Jagannath C. 2001. A role for complement C5 in organism containment and granulomatous response during murine tuberculosis. Scand J Immunol 53(5):464-74. PubMed: 11309154MGI: J:103981
- Addis-Lieser E; Kohl J; Chiaramonte MG. 2005. Opposing regulatory roles of complement factor 5 in the development of bleomycin-induced pulmonary fibrosis. J Immunol 175(3):1894-902. PubMed: 16034133MGI: J:107269
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- Barthlott T; Stockinger B. 2001. Lineage fate alteration of thymocytes developing in an MHC environment containing MHC/peptide ligands with antagonist properties. Eur J Immunol 31(12):3595-601. PubMed: 11745379MGI: J:151748
- Baudino L; Sardini A; Ruseva MM; Fossati-Jimack L; Cook HT; Scott D; Simpson E; Botto M. 2014. C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. Proc Natl Acad Sci U S A 111(4):1503-8. PubMed: 24474777MGI: J:206648
- Bauer K; Yu X; Wernhoff P; Koczan D; Thiesen HJ; Ibrahim SM. 2004. Identification of new quantitative trait loci in mice with collagen-induced arthritis. Arthritis Rheum 50(11):3721-8. PubMed: 15529344MGI: J:94347
- Binstadt BA; Hebert JL; Ortiz-Lopez A; Bronson R; Benoist C; Mathis D. 2009. The same systemic autoimmune disease provokes arthritis and endocarditis via distinct mechanisms. Proc Natl Acad Sci U S A 106(39):16758-63. PubMed: 19805369MGI: J:153217
- Bode J; Dutow P; Sommer K; Janik K; Glage S; Tummler B; Munder A; Laudeley R; Sachse KW; Klos A. 2012. A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. PLoS One 7(11):e50327. PubMed: 23189195MGI: J:194784
- Bora NS; Kaliappan S; Jha P; Xu Q; Sohn JH; Dhaulakhandi DB; Kaplan HJ; Bora PS. 2006. Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H. J Immunol 177(3):1872-8. PubMed: 16849499MGI: J:138026
- Borders CW; Courtney A; Ronen K; Pilar Laborde-Lahoz M; Guidry TV; Hwang SA; Olsen M; Hunter RL Jr; Hollmann TJ; Wetsel RA; Actor JK. 2005. Requisite role for complement C5 and the C5a receptor in granulomatous response to mycobacterial glycolipid trehalose 6,6'-dimycolate. Scand J Immunol 62(2):123-30. PubMed: 16101818MGI: J:114316
- 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: 22952717MGI: J:191663
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- Hillebrandt S; Wasmuth HE; Weiskirchen R; Hellerbrand C; Keppeler H; Werth A; Schirin-Sokhan R; Wilkens G; Geier A; Lorenzen J; Kohl J; Gressner AM; Matern S; Lammert F. 2005. Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans. Nat Genet 37(8):835-43. PubMed: 15995705MGI: J:100159
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