Overview

Also Known As:Sod1 KO

Homozygous Sod1^tm1Leb knock-out mice are characterized by abnormal retinal and cochlear ganglions, and they have age-related defects in hearing, vasculature, and muscle. These mice may be useful in studying retinal dysfunction, autoimmunity, female reproductive development/function, glaucoma, hearing loss, Alzheimer's Disease, familial amyotrophic lateral sclerosis (ALS), and other age-related disorders.

Genetic overview

Genetic Background	Generation

Sod1^tm1Leb

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Sod1	superoxide dismutase 1, soluble

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Research Applications

Metabolism Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Sod1^tm1Leb (formerly SOD1^m1BCM) knock-out allele disrupts exons 1 and 2 of the Cu,Zn-superoxide dismutase-1 gene (Sod1). This knock-out allele is the same as carried by B6;129S-Sod1^tm1Leb/J (Stock No. 002972) but is fully congenic in the present strain having been backcrossed to C57BL/6JEi for 13 generations. In the original strain no protein expression from the targeted locus is detected in brain tissues. Heterozygous mice are viable and fertile. While homozygous males reproduce normally, homozygous females are infertile. Homozygous mice have abnormalities of the retinal ganglion, cochlear ganglion, and female reproductive development/function. Homozygous mice also exhibit age-related deafness, accelerated vascular aging and age-related skeletal muscle defects. These mutant mice may be useful in studying retinal dysfunction, autoimmunity, glaucoma, hearing loss, Alzheimer's Disease, familial amyotrophic lateral sclerosis (ALS), and other age-related disorders.

Development

This strain was generated in the Laboratory of Muriel Davisson by backcrossing the Sod1^tm1Leb mutation from the segregating B6;129S7 background onto the C57BL/6JEi strain for 13 generations. The backcrossing was begun in 1998. In 2004 embryos were generated for cryopreservation via in vitro fertilization using C57BL/6J females and heterozygous males at generation N13.

Genetics

Sod1^tm1Leb

Allele Symbol: Sod1^tm1Leb

Allele Name	targeted mutation 1, Russell M Lebovitz
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Cu,Zn-SOD^-; CuZnSOD-; SOD1^-; SOD1^m1BCM
Gene Symbol and Name	Sod1, superoxide dismutase 1, soluble
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	16
Molecular Note	Replacement of exons 1 and 2 with a PGK-hprt expression cassette. Protein was not detected in brain of homozygous mutant mice.
Mutations Made By	Dr. Russell Lebovitz, SUMA Partners

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

low tension glaucoma

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

dry eye syndrome

Research Areas By Phenotype

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

Genotype: Sod1^tm1Leb related

Metabolism Research
Neurobiology Research
- Metabolic Defects
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Sod1^tm1Leb/Sod1^tm1Leb
involves: 129S7/SvEvBrd * C57BL/6

endocrine/exocrine gland phenotype

Meibomian gland inflammation
- increase in periglandular inflammatory infiltrates from 10 to 50 weeks of age

abnormal Meibomian gland acinus morphology
- decrease in meibomian gland glandular acinar density from 10 to 50 weeks of age
- accumulation of large lipid droplets in the acinar units of meibomian glands of 50 weeks of age; lipid droplets become larger in size and increase in number from 10 to 50 weeks of age

abnormal ovary morphology
- at 12 weeks of age, increased stromal cell proliferation is noted in the center of the mutant ovary

decreased corpora lutea number

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

small ovary
- homozygous mutant ovaries are often smaller than wild-type ovaries

abnormal Meibomian gland physiology
- increase in apoptosis within the meibomian glands at 50 weeks of age

abnormal Meibomian gland morphology
- increase in periglandular fibrosis from 10 to 50 weeks of age

impaired ovarian folliculogenesis
- at 6-12 weeks of age, female homozygotes show limited follicular development beyond the early antral follicle stage

homeostasis/metabolism phenotype

increased circulating interleukin-6 level
- increase in the mean serum IL-6 concentration from 10 to 50 weeks of age

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

increased circulating tumor necrosis factor level
- increase in serum TNF-alpha levels from 10 weeks of age

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

cellular phenotype

dilated mitochondria
- in 50 week old mice

abnormal mitochondrial morphology
- mitochondrial swelling, disorientation, shortening, and disorganization of cristae are seen in 80% of 50 week old mice compared to 40% of wild-type mice at this age

disorganized mitochondrial cristae
- in 50 week old mice

oxidative stress
- mice exhibit changes in oxidative stress markers in the meibomian glands

immune system phenotype

blepharitis
- mice exhibit changes in tear, serum and eye lid tissue inflammatory markers
- eyelid inflammation

increased circulating tumor necrosis factor level
- increase in serum TNF-alpha levels from 10 weeks of age

increased tumor necrosis factor secretion
- increase in mean tear TNF-alpha concentration from 10 to 50 weeks of age

increased interleukin-6 secretion
- increase in tear IL-6 concentration from 10 to 50 weeks of age

increased circulating interleukin-6 level
- increase in the mean serum IL-6 concentration from 10 to 50 weeks of age

Meibomian gland inflammation
- increase in periglandular inflammatory infiltrates from 10 to 50 weeks of age

integument phenotype

abnormal Meibomian gland acinus morphology
- accumulation of large lipid droplets in the acinar units of meibomian glands of 50 weeks of age; lipid droplets become larger in size and increase in number from 10 to 50 weeks of age
- decrease in meibomian gland glandular acinar density from 10 to 50 weeks of age

abnormal Meibomian gland physiology
- increase in apoptosis within the meibomian glands at 50 weeks of age

abnormal Meibomian gland morphology
- increase in periglandular fibrosis from 10 to 50 weeks of age

Meibomian gland inflammation
- increase in periglandular inflammatory infiltrates from 10 to 50 weeks of age

reproductive system phenotype

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

small ovary
- homozygous mutant ovaries are often smaller than wild-type ovaries

decreased corpora lutea number

impaired ovarian folliculogenesis
- at 6-12 weeks of age, female homozygotes show limited follicular development beyond the early antral follicle stage

reduced female fertility
- female homozygotes survive to adulthood and appear to show normal sexual differentiation but are subfertile
- Normal - however, mutant and control females were shown to produce a similar number of eggs upon pharmacological superovulation
- Normal - in contrast to females, male homozygotes are fertile with normal testicular morphology
- 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

female infertility
- 5 of 16 female homozygotes failed to become pregnant over a 2-6 month period

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)

abnormal ovary morphology
- at 12 weeks of age, increased stromal cell proliferation is noted in the center of the mutant ovary

vision/eye phenotype

abnormal Meibomian gland acinus morphology
- decrease in meibomian gland glandular acinar density from 10 to 50 weeks of age
- accumulation of large lipid droplets in the acinar units of meibomian glands of 50 weeks of age; lipid droplets become larger in size and increase in number from 10 to 50 weeks of age

abnormal Meibomian gland morphology
- increase in periglandular fibrosis from 10 to 50 weeks of age

blepharitis
- eyelid inflammation
- mice exhibit changes in tear, serum and eye lid tissue inflammatory markers

decreased tear production
- mean weight adjusted aqueous tear production is lower at 10 and 50 weeks of age and mice show a significant decrease in tear quantity from 10 to 50 weeks of age

Meibomian gland inflammation
- increase in periglandular inflammatory infiltrates from 10 to 50 weeks of age

abnormal corneal epithelium morphology
- mean corneal vital staining score is worse at 10 and 50 weeks of age indicating ocular surface epithelial cell damage

abnormal tear production
- lower tear break up time is seen at 50 weeks of age compared to wild-type mice indicating decreased tear stability

Genotype: Sod1^tm1Leb/Sod1^tm1Leb
B6;129S-Sod1/J

vision/eye phenotype

abnormal eye electrophysiology
- Normal - however, the intraocular pressure is normal
- the amplitude of pattern electroretinogram (ERG) is reduced in 24 week old mutants, although dark-adapted and cone ERGs show no impairment, indicating impaired function of retinal ganglion cells

abnormal retinal nerve fiber layer morphology
- 24 week old mutants exhibit thinning of the nerve fiber layer

abnormal retinal ganglion layer morphology
- level of reactive oxygen species (ROS) in the retinal ganglion cell layer is higher in 24-week old mutants than in wild-type mice

decreased retinal ganglion cell number
- number of cells in the retinal ganglion cell layer is reduced in 24 week old mutants but not at 8 weeks of age, indicating a progressive reduction
- Normal - however, photoreceptor cell death is not seen at 24 weeks of age

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- 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
- 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

thin stria vascularis
- at 15 months, homozygotes display a significantly thinner stria vascularis in the apical turn relative to heterozygous or wild-type mice
- however, no differences in stria vascularis thickness are noted in the apical turn at 7-9 months

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

nervous system phenotype

decreased retinal ganglion cell number
- number of cells in the retinal ganglion cell layer is reduced in 24 week old mutants but not at 8 weeks of age, indicating a progressive reduction
- Normal - however, photoreceptor cell death is not seen at 24 weeks of age

cochlear ganglion degeneration
- in homozygotes, the magnitude of ganglion cell loss is greater than that of C57BL/6 control mice, esp. above the basal turn
- starting at 7-9 months, homozygotes display severe progressive degeneration of spiral ganglion cells in all cochlear turns

Genotype: Sod1^tm1Leb/Sod1^tm1Leb
involves: 129S7/SvEvBrd-Hprt * C57BL/6

vision/eye phenotype

decreased b-wave amplitude
- with scotopic and photopic ERG at age 42 and 81 weeks

thin retinal outer nuclear layer
- progressive age-related thinning from age 30 weeks

decreased a-wave amplitude
- with scotopic and photopic ERG at age 42 and 81 weeks

thin retinal inner nuclear layer
- progressive age-related thinning from age 30 weeks

disorganized retinal inner nuclear layer
- swollen nuclei, vacuolized cytoplasm and disrupted plasma and nuclear membranes in 15-month-old senescent mice

disorganized retinal outer nuclear layer
- decreased density, swollen cell bodies and damaged mitochondria in 15-month-old senescent mice

Genotype: Sod1^tm1Leb/Sod1⁺
B6;129S-Sod1/J

nervous system phenotype

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

References

Additional - Sod1^tm1Leb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Human HPRT
- Standard PCR:Sod1
- Genotyping resources and troubleshooting
Citation
When using the Sod1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003881 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Sod1<tm1Leb>

Related Products and Services

Frozen Mouse Embryo	B6.129S7-Sod1<tm1Leb>/DnJ Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S7-Sod1<tm1Leb>/DnJ Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S7-Sod1<tm1Leb>/DnJ Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129S7-Sod1<tm1Leb>/DnJ Frozen Embryos	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Licensing Information

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Email: TechTran@jax.org

Also Known As:Sod1 KO

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Sod1tm1Leb

Allele Symbol: Sod1tm1Leb

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Sod1tm1Leb related

Mammalian Phenotype Terms by Genotype

Genotype: Sod1tm1Leb/Sod1tm1Lebinvolves: 129S7/SvEvBrd * C57BL/6

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

integument phenotype

reproductive system phenotype

vision/eye phenotype

Genotype: Sod1tm1Leb/Sod1tm1LebB6;129S-Sod1/J

vision/eye phenotype

hearing/vestibular/ear phenotype

nervous system phenotype

Genotype: Sod1tm1Leb/Sod1tm1Lebinvolves: 129S7/SvEvBrd-Hprt * C57BL/6

vision/eye phenotype

Genotype: Sod1tm1Leb/Sod1+B6;129S-Sod1/J

nervous system phenotype

References

Additional - Sod1tm1Leb related

Genotyping Protocols

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Sod1^tm1Leb

Allele Symbol: Sod1^tm1Leb

Genotype: Sod1^tm1Leb related

Genotype: Sod1^tm1Leb/Sod1^tm1Leb
involves: 129S7/SvEvBrd * C57BL/6

Genotype: Sod1^tm1Leb/Sod1^tm1Leb
B6;129S-Sod1/J

Genotype: Sod1^tm1Leb/Sod1^tm1Leb
involves: 129S7/SvEvBrd-Hprt * C57BL/6

Genotype: Sod1^tm1Leb/Sod1⁺
B6;129S-Sod1/J

Additional - Sod1^tm1Leb related