Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation {F?+8p}N2F11 (13-JAN-09) Generation Definitions   Donating Investigator Russell Lebovitz,   SUMA Partners

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Sod1^tm1Leb targeted mutation produce no SOD1 protein. Female homozygous mice are infertile, while male homozygous mice reproduce normally.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Sod1^tm1Leb allele

003881

B6.129S7-Sod1tm1Leb/DnJ

View Strains carrying   Sod1^tm1Leb     (1 strain)

Strains carrying other alleles of Sod1

003881	B6.129S7-Sod1tm1Leb/DnJ
004140	B6.SOD1-Sod1c/CjeDnJ
005110	FVB-Tg(Sod1*G86R)M1Jwg/J

View Strains carrying other alleles of Sod1     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Sod1^tm1Leb/Sod1⁺

        B6;129S7-Sod1^tm1Leb/J

• nervous system phenotype
• cochlear ganglion degeneration
  • contrary to previous findings, heterozygotes display no significant differences in ABR thresholds relative to wild-type mice at any age or any frequency tested   (MGI Ref ID J:102419)
  • no degenerative changes are noted in the heterozygous stria vascularis even at 18 months of age   (MGI Ref ID J:102419)
  • however, unlike wild-type mice, aging heterozygotes show a decrease in ganglion cell density at 15 months   (MGI Ref ID J:102419)

Sod1^tm1Leb/Sod1^tm1Leb

        B6;129S7-Sod1^tm1Leb/J

• hearing/vestibular/ear phenotype
• deafness
  • at 12 and 15 months, homozygotes exhibit an earlier and significantly greater hearing loss than age-matched C57BL/6, wild-type or heterozygous mice   (MGI Ref ID J:102419)
• decreased brainstem auditory evoked potential
  • at 12 and 15 months, homozygotes exhibit significantly increased ABR thresholds for clicks and tone pip stimuli at 8, 16 and 32 kHz relative to C57BL/6, wild-type or heterozygous mice; however, no differences are noted at 7-9 months   (MGI Ref ID J:102419)
  • at 12 months, homozygotes show an ~20 dB elevation in ABR thresholds at 32 kHz relative to C57BL/6 control mice; the latter have ABR thresholds that are ~10 dB higher than those in wild-type or heterozygous mice   (MGI Ref ID J:102419)
• thin stria vascularis
  • at 15 months, homozygotes display a significantly thinner stria vascularis in the apical turn relative to heterozygous or wild-type mice   (MGI Ref ID J:102419)
  • however, no differences in stria vascularis thickness are noted in the apical turn at 7-9 months   (MGI Ref ID J:102419)
• nervous system phenotype
• cochlear ganglion degeneration
  • starting at 7-9 months, homozygotes display severe progressive degeneration of spiral ganglion cells in all cochlear turns   (MGI Ref ID J:102419)
  • in homozygotes, the magnitude of ganglion cell loss is greater than that of C57BL/6 control mice, esp. above the basal turn   (MGI Ref ID J:102419)

Sod1^tm1Leb/Sod1^tm1Leb

        involves: 129S7/SvEvBrd * C57BL/6

• reproductive system phenotype
• abnormal ovary morphology
  • at 12 weeks of age, increased stromal cell proliferation is noted in the center of the mutant ovary   (MGI Ref ID J:64299)
• • decreased corpora lutea number   (MGI Ref ID J:64299)
  • decreased mature ovarian follicle number
    • while normal-appearing primary follicles and some small antral follicles are present, only a few large antral follicles and corpora lutea are observed   (MGI Ref ID J:64299)
  • impaired ovarian folliculogenesis
    • at 6-12 weeks of age, female homozygotes show limited follicular development beyond the early antral follicle stage   (MGI Ref ID J:64299)
  • small ovary
    • homozygous mutant ovaries are often smaller than wild-type ovaries   (MGI Ref ID J:64299)
• decreased litter size
  • over a 2-6 month period, female homozygotes produced a significantly decreased average litter size relative to female heterozygotes (2.7 vs 8.6 offspring/litter, respectively)   (MGI Ref ID J:64299)
• female infertility
  • 5 of 16 female homozygotes failed to become pregnant over a 2-6 month period   (MGI Ref ID J:64299)
• reduced female fertility
  • female homozygotes survive to adulthood and appear to show normal sexual differentiation but are subfertile   (MGI Ref ID J:64299)
  • whereas breeding of 5 female heterozygotes with male heterozygotes over a 6 month period produced an average of 1.0 litter/month, only 11 of 16 female homozygotes became pregnant over a 2-6 month period averaging 0.23 litters/month   (MGI Ref ID J:64299)
  • however, mutant and control females were shown to produce a similar number of eggs upon pharmacological superovulation   (MGI Ref ID J:64299)
  • in contrast to females, male homozygotes are fertile with normal testicular morphology   (MGI Ref ID J:64299)
• endocrine/exocrine gland phenotype
• abnormal ovary morphology
  • at 12 weeks of age, increased stromal cell proliferation is noted in the center of the mutant ovary   (MGI Ref ID J:64299)
• • decreased corpora lutea number   (MGI Ref ID J:64299)
  • decreased mature ovarian follicle number
    • while normal-appearing primary follicles and some small antral follicles are present, only a few large antral follicles and corpora lutea are observed   (MGI Ref ID J:64299)
  • impaired ovarian folliculogenesis
    • at 6-12 weeks of age, female homozygotes show limited follicular development beyond the early antral follicle stage   (MGI Ref ID J:64299)
  • small ovary
    • homozygous mutant ovaries are often smaller than wild-type ovaries   (MGI Ref ID J:64299)
• homeostasis/metabolism phenotype
• decreased circulating luteinizing hormone level
  • adult female homozygotes exhibit suppressed serum LH levels relative to control females (17.4 +/- 3.0 ng/ml vs 57.8 +/- 17.7 ng/ml, respectively), as shown by RIA analysis   (MGI Ref ID J:64299)
• suppressed circulating follicle stimulating hormone level
  • adult female homozygotes exhibit suppressed serum FSH levels relative to control females (38.5 +/- 3.1 ng/ml vs 105.0 +/- 17.3 ng/ml, respectively), as shown by RIA analysis   (MGI Ref ID J:64299)

View Research Applications

Research Applications

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

Sod1^tm1Leb related

Metabolism Research

Neurobiology Research
Metabolic Defects
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Sod1tm1Leb
Allele Name		targeted mutation 1, Russell M Lebovitz
Allele Type		Targeted (knock-out)
Common Name(s)		Cu,Zn-SOD-; CuZnSOD-; SOD1-; SOD1m1BCM;
Mutation Made By		Russell Lebovitz,   SUMA Partners
Strain of Origin		129S7/SvEvBrd-Hprt
ES Cell Line Name		AB2.1
ES Cell Line Strain		129S7/SvEvBrd-Hprt
Gene Symbol and Name		Sod1, superoxide dismutase 1, soluble
Chromosome		16
Gene Common Name(s)		ALS; ALS1; B430204E11Rik; Cu(2+)-Zn2+ superoxide dismutase; Cu/Zn-SOD; CuZnSOD; IPOA; Ipo-1; Ipo1; RIKEN cDNA B430204E11 gene; SOD; SODC; Sod-1; hSod1; homodimer; indophenol oxidase;
Molecular Note		Replacement of exons 1 and 2 with a PGK-hprt expression cassette. Protein was not detected in brain of homozygous mutant mice. [MGI Ref ID J:64299]

Genotyping

Genotyping Information

Genotyping Protocols

Sod1^tm1Leb, Melt Curve Analysis

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Matzuk MM; Dionne L; Guo Q; Kumar TR; Lebovitz RM. 1998. Ovarian function in superoxide dismutase 1 and 2 knockout mice. Endocrinology 139(9):4008-11. [PubMed: 9724058]  [MGI Ref ID J:64299]

Additional References

Morikawa K; Shimokawa H; Matoba T; Kubota H; Akaike T; Talukder MA; Hatanaka M; Fujiki T; Maeda H; Takahashi S; Takeshita A. 2003. Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization. J Clin Invest 112(12):1871-9. [PubMed: 14679182]  [MGI Ref ID J:86950]

Sod1^tm1Leb related

Asimakis GK; Lick S; Patterson C. 2002. Postischemic recovery of contractile function is impaired in SOD2(+/-) but not SOD1(+/-) mouse hearts. Circulation 105(8):981-6. [PubMed: 11864929]  [MGI Ref ID J:103317]

Baumbach GL; Didion SP; Faraci FM. 2006. Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase. Stroke 37(7):1850-5. [PubMed: 16763183]  [MGI Ref ID J:136409]

Carlstrom M; Brown RD; Sallstrom J; Larsson E; Zilmer M; Zabihi S; Eriksson UJ; Persson AE. 2009. SOD1 deficiency causes salt sensitivity and aggravates hypertension in hydronephrosis. Am J Physiol Regul Integr Comp Physiol 297(1):R82-92. [PubMed: 19403858]  [MGI Ref ID J:150216]

Cooke CL; Davidge ST. 2003. Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice. Cardiovasc Res 60(3):635-42. [PubMed: 14659809]  [MGI Ref ID J:162746]

Didion SP; Kinzenbaw DA; Faraci FM. 2005. Critical role for CuZn-superoxide dismutase in preventing angiotensin II-induced endothelial dysfunction. Hypertension 46(5):1147-53. [PubMed: 16216984]  [MGI Ref ID J:135455]

Didion SP; Ryan MJ; Didion LA; Fegan PE; Sigmund CD; Faraci FM. 2002. Increased superoxide and vascular dysfunction in CuZnSOD-deficient mice. Circ Res 91(10):938-44. [PubMed: 12433839]  [MGI Ref ID J:109001]

Groleau J; Dussault S; Turgeon J; Haddad P; Rivard A. 2011. Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization. PLoS One 6(8):e23308. [PubMed: 21858065]  [MGI Ref ID J:176492]

Harraz MM; Marden JJ; Zhou W; Zhang Y; Williams A; Sharov VS; Nelson K; Luo M; Paulson H; Schoneich C; Engelhardt JF. 2008. SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest 118(2):659-70. [PubMed: 18219391]  [MGI Ref ID J:131850]

Hashizume K; Hirasawa M; Imamura Y; Noda S; Shimizu T; Shinoda K; Kurihara T; Noda K; Ozawa Y; Ishida S; Miyake Y; Shirasawa T; Tsubota K. 2008. Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. Am J Pathol 172(5):1325-31. [PubMed: 18372426]  [MGI Ref ID J:134267]

Imamura Y; Noda S; Hashizume K; Shinoda K; Yamaguchi M; Uchiyama S; Shimizu T; Mizushima Y; Shirasawa T; Tsubota K. 2006. Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc Natl Acad Sci U S A 103(30):11282-7. [PubMed: 16844785]  [MGI Ref ID J:111796]

Ishii T; Matsuki S; Iuchi Y; Okada F; Toyosaki S; Tomita Y; Ikeda Y; Fujii J. 2005. Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress. Free Radic Res 39(7):697-705. [PubMed: 16036348]  [MGI Ref ID J:114348]

Iuchi Y; Kibe N; Tsunoda S; Suzuki S; Mikami T; Okada F; Uchida K; Fujii J. 2010. Implication of oxidative stress as a cause of autoimmune hemolytic anemia in NZB mice. Free Radic Biol Med 48(7):935-44. [PubMed: 20079426]  [MGI Ref ID J:158021]

Iuchi Y; Okada F; Onuma K; Onoda T; Asao H; Kobayashi M; Fujii J. 2007. Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production. Biochem J 402(2):219-27. [PubMed: 17059387]  [MGI Ref ID J:118550]

Iuchi Y; Okada F; Takamiya R; Kibe N; Tsunoda S; Nakajima O; Toyoda K; Nagae R; Suematsu M; Soga T; Uchida K; Fujii J. 2009. Rescue of anaemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes. Biochem J 422(2):313-20. [PubMed: 19515016]  [MGI Ref ID J:154894]

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]

Keithley EM; Canto C; Zheng QY; Wang X; Fischel-Ghodsian N; Johnson KR. 2005. Cu/Zn superoxide dismutase and age-related hearing loss. Hear Res 209(1-2):76-85. [PubMed: 16055286]  [MGI Ref ID J:102419]

Kessova IG; Cederbaum AI. 2007. Mitochondrial alterations in livers of Sod1-/- mice fed alcohol. Free Radic Biol Med 42(10):1470-80. [PubMed: 17448893]  [MGI Ref ID J:121616]

Kostrominova TY. 2010. Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice. Free Radic Biol Med 49(10):1582-93. [PubMed: 20800676]  [MGI Ref ID J:165857]

Kubota M; Shimmura S; Kubota S; Miyashita H; Kato N; Noda K; Ozawa Y; Usui T; Ishida S; Umezawa K; Kurihara T; Tsubota K. 2011. Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model. Invest Ophthalmol Vis Sci 52(1):427-33. [PubMed: 20847117]  [MGI Ref ID J:171558]

Meissner F; Molawi K; Zychlinsky A. 2008. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 9(8):866-72. [PubMed: 18604212]  [MGI Ref ID J:137865]

Morikawa K; Shimokawa H; Matoba T; Kubota H; Akaike T; Talukder MA; Hatanaka M; Fujiki T; Maeda H; Takahashi S; Takeshita A. 2003. Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization. J Clin Invest 112(12):1871-9. [PubMed: 14679182]  [MGI Ref ID J:86950]

Murakami K; Inagaki J; Saito M; Ikeda Y; Tsuda C; Noda Y; Kawakami S; Shirasawa T; Shimizu T. 2009. Skin atrophy in cytoplasmic SOD-deficient mice and its complete recovery using a vitamin C derivative. Biochem Biophys Res Commun 382(2):457-61. [PubMed: 19289104]  [MGI Ref ID J:148029]

Murakami K; Murata N; Noda Y; Tahara S; Kaneko T; Kinoshita N; Hatsuta H; Murayama S; Barnham KJ; Irie K; Shirasawa T; Shimizu T. 2011. SOD1 (Copper/Zinc Superoxide Dismutase) Deficiency Drives Amyloid beta Protein Oligomerization and Memory Loss in Mouse Model of Alzheimer Disease. J Biol Chem 286(52):44557-68. [PubMed: 22072713]  [MGI Ref ID J:178835]

Starzynski RR; Canonne-Hergaux F; Willemetz A; Gralak MA; Wolinski J; Stys A; Olszak J; Lipinski P. 2009. Haemolytic anaemia and alterations in hepatic iron metabolism in aged mice lacking Cu,Zn-superoxide dismutase. Biochem J 420(3):383-90. [PubMed: 19296829]  [MGI Ref ID J:151021]

Starzynski RR; Lipinski P; Drapier JC; Diet A; Smuda E; Bartlomiejczyk T; Gralak MA; Kruszewski M. 2005. Down-regulation of iron regulatory protein 1 activities and expression in superoxide dismutase 1 knock-out mice is not associated with alterations in iron metabolism. J Biol Chem 280(6):4207-12. [PubMed: 15557328]  [MGI Ref ID J:96864]

Usui S; Oveson BC; Iwase T; Lu L; Lee SY; Jo YJ; Wu Z; Choi EY; Samulski RJ; Campochiaro PA. 2011. Overexpression of SOD in retina: Need for increase in H(2)O(2)-detoxifying enzyme in same cellular compartment. Free Radic Biol Med 51(7):1347-54. [PubMed: 21736939]  [MGI Ref ID J:175696]

Yada T; Shimokawa H; Morikawa K; Takaki A; Shinozaki Y; Mori H; Goto M; Ogasawara Y; Kajiya F. 2008. Role of Cu,Zn-SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo. Am J Physiol Heart Circ Physiol 294(1):H441-8. [PubMed: 18024543]  [MGI Ref ID J:132306]

Ziv S; Brenner O; Amariglio N; Smorodinsky NI; Galron R; Carrion DV; Zhang W; Sharma GG; Pandita RK; Agarwal M; Elkon R; Katzin N; Bar-Am I; Pandita TK; Kucherlapati R; Rechavi G; Shiloh Y; Barzilai A. 2005. Impaired genomic stability and increased oxidative stress exacerbate different features of Ataxia-telangiectasia. Hum Mol Genet 14(19):2929-43. [PubMed: 16150740]  [MGI Ref ID J:101745]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Mating System	Heterozygote x Heterozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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