Overview

Also Known As: Sod1 KO

This strain is currently unavailable due to replenishing of cryopreserved stocks.

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

View Genetics

Research Applications

Metabolism Research
Neurobiology Research

View All Research Applications

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)	Sod1^tm1Leb; targeted mutation 1, Russell M Lebovitz
Gene Symbol and Name	Sod1, superoxide dismutase 1, soluble
Gene Synonym(s)	B430204E11Rik; ALS; ALS1; Ipo-1; Ipo1; Sod-1; HEL-S-44; hSod1; Ipo-1; Ipo1; IPOA; Cu/Zn-SOD; homodimer; SOD; Sod-1; SODC; Cu(2+)-Zn2+ superoxide dismutase; CuZnSOD; B430204E11Rik; indophenol oxidase; RIKEN cDNA B430204E11 gene; STAHP
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 Genotype

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
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

References

Additional - Sod1^tm1Leb related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Sod1^tm1Leb
- Standard PCR:Sod1^tm1Leb
- 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.

Strain Interest Registration

Please fill out the form below to indicate your interest in purchasing this JAX®Mice strain.
This information helps us manage the colony build and better meet the broad needs of the research community.
Please send any technical questions to Technical Support.

Contact Information

First Name

First name is required

Last Name

Last name is required

Institution

Institution is Required

Phone Number

Phone Number is required

Email

Email is required

Interest

Please indicate your approximate levels of interest. You can add another line by selecting "Add More Interest".

Number of Mice

Frequency

Product

Comment

Terms Of Use

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

Genetic overview

Research Applications

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 Genotype

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

References

Additional - Sod1tm1Leb related

Genotyping Protocols

Citation

Strain Interest Registration

Contact Information

Interest

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

Additional - Sod1^tm1Leb related