Overview

Also Known As:Sod1 KO

Homozygous SOD1^m1BCM 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.

Donating Investigator

Dr. Russell Lebovitz, SUMA Partners

Genetic overview

Genetic Background	Generation

Sod1^tm1Leb

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

View Genetics

Research Applications

Sensorineural Research
Mouse/Human Gene Homologs
Metabolism Research
Neurobiology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

The SOD1^m1BCM knock-out allele disrupts exons 1 and 2 of the Cu,Zn-superoxide dismutase-1 gene (Sod1). 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

A targeting construct was designed to delete exons 1 and 2 of the Cu,Zn-superoxide dismutase-1 gene (Sod1) and replace those exons with a PGK-HPRT expression cassette. This construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2-derived AB2.1 embryonic stem (ES) cells. The resulting mutant mice (SOD1^m1BCM) were on a mixed C57BL/6;129SvEv genetic background when they arrived at The Jackson Laboratory Repository in 1997. Upon arrival, mutant mice were bred together, and then to B6129SF1/J (Stock No. 101043) for one generation. After this, heterozygous mice were bred together to maintain the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

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

View All References

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:

Sensorineural Research
- Eye Defects
  - hereditary glaucoma
Mouse/Human Gene Homologs
- deafness

Genotype: Sod1^tm1Leb related

Metabolism Research
Neurobiology Research
- Metabolic Defects
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

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

increased or absent threshold for auditory brainstem response
- 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
- 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

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

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 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

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

decreased retinal ganglion cell number
- Normal - however, photoreceptor cell death is not seen at 24 weeks of age
- 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

nervous system phenotype

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

decreased retinal ganglion cell number
- Normal - however, photoreceptor cell death is not seen at 24 weeks of age
- 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

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

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

cellular phenotype

abnormal mitochondrion 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

dilated mitochondria
- in 50 week old mice

disorganized mitochondrial cristae
- in 50 week old mice

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

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

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

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

immune system phenotype

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

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

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

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

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

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

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

reproductive system phenotype

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 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)

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

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

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

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

vision/eye phenotype

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

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

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

endocrine/exocrine gland 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 morphology
- increase in periglandular fibrosis from 10 to 50 weeks of age

abnormal Meibomian gland physiology
- increase in apoptosis within the meibomian glands at 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

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

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

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

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

vision/eye phenotype

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

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

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

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

References

Matzuk MM; Dionne L; Guo Q; Kumar TR; Lebovitz RM. 1998. Ovarian function in superoxide dismutase 1 and 2 knockout mice. Endocrinology 139(9):4008-11PubMed: 9724058 MGI: 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):1871-9PubMed: 14679182 MGI: J:86950

Additional - Sod1^tm1Leb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Sod1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice are bred together, or heterozygous females are bred to homozygous males. Female homozygous mice are infertile, though male homozygous mice reproduce normally. Average litter size is observed. Expected coat color from breeding is white bellied agouti or black.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the Sod1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002972 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
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Sod1<tm1Leb>

Related Products and Services

Frozen Mouse Embryo	B6;129S-Sod1<tm1Leb>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129S-Sod1<tm1Leb>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129S-Sod1<tm1Leb>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6;129S-Sod1<tm1Leb>/J Frozen Embryos	$3373.50

Payment Terms and Conditions

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.

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:Sod1 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

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/Sod1tm1LebB6;129S-Sod1/J

hearing/vestibular/ear phenotype

vision/eye phenotype

nervous system phenotype

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

nervous system phenotype

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

cellular phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

reproductive system phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

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

vision/eye phenotype

References

Additional References

Additional - Sod1tm1Leb related

Genotyping Protocols

Breeding Considerations

Appearance

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Sod1^tm1Leb

Allele Symbol: Sod1^tm1Leb

Genotype: Sod1^tm1Leb related

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

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

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

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

Additional - Sod1^tm1Leb related