Overview

This recessive mutation causes early onset photoreceptor degeneration, leukoencephalopathy, and azoospermia.

Donating Investigator

Kevin Seburn, JAX

Genetic overview

Genetic Background	Generation

Clcn2^nmf240

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Clcn2	chloride channel, voltage-sensitive 2

View Genetics

Research Applications

Sensorineural Research
Reproductive Biology Research
Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Homozygotes exhibit grainy retinas by 3 weeks of age which progresses into large white patches distributed across the entire retina by 12 weeks of age. At 10 days of age the apical processes of the retinal pigment epithelium are abnormally elongated, by 14 days of age the retinal outer nuclear layer is reduced in thickness and contains pyknotic nuclei and the photoreceptor outer segments are disorganized and shortened. Standard pathology work-up on two male mutants (145 or 224 days of age) revealed severe bilateral retinal degeneration.

By 3 weeks of age the photoreceptor layer is reduced to one to two layers of cells and the outer segments are not visible. Both dark and light adapted flash electroretinograms show reduced amplitude responses as early as 14 days of age and this worsens progressively to near zero by 26 days of age.

Male infertility is associated with decreased weight of the testes and epididymides and azoospermia as early as 6 weeks of age with severe degradation of spermatogenesis.

Progressive leukoencephalopathy is also found, with vacuoles in the white matter tracts and cerebellum by 7 months of age becoming more severe at 18 months of age. Despite these histological findings, accompanying behavioral abnormalities have not been found.

Development

A C57BL/6J male was treated with N-ethyl-N-nitrosurea, bred to C57BL/6J females, an F1 male offspring was bred with a C57BL/6J female, and a female from the resulting offspring was backcrossed to its F1 grandfather to generate a population in which recessive mutations could be phenotypically identified. This mutation has been maintained on the C57BL/6J background.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Clcn2^nmf240

Allele Symbol: Clcn2^nmf240

Allele Name	neuroscience mutagenesis facility, 240
Allele Type	Chemically induced (ENU)
Allele Synonym(s)
Gene Symbol and Name	Clcn2, chloride channel, voltage-sensitive 2
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	16
Molecular Note	This mutation was discovered in a mutagenesis screen. A C-T nonsense mutation at base pair 1063 is predicted to result in the glutamine at amino acid 355 in the encoded protein modified to a stop codon.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Clcn2^nmf240 related

Sensorineural Research
- Retinal Degeneration
- Eye Defects
Reproductive Biology Research
- Developmental Defects Affecting Gonads
  - males only
  - germ cell deficient
- Fertility Defects
  - males only
Neurobiology Research
- Neuroscience Mutagenesis Facility Strain
- Cerebellar Defects
- Neurodegeneration
Research Tools
- Sensorineural Research
  - retinal degeneration

Mammalian Phenotype Terms by Genotype

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

Genotype: Clcn2^nmf240/Clcn2^nmf240
C57BL/6J-Clcn2/J

cellular phenotype

azoospermia
- by 20 weeks of age homozygotes have only a few spermatogonial stem cells, although Sertoli cells remain
- even as early as 6 weeks of age homozygotes are azoospermic with severe degradation of spermatogenesis and are devoid of spermatocytes, spermatids, and spermatozoa with elongated tails

vision/eye phenotype

abnormal cone electrophysiology

abnormal eye electrophysiology
- both dark and light adapted flash electroretinograms show reduced amplitude responses as early as 14 days of age progressing to near zero by 26 days of age

abnormal photoreceptor outer segment morphology
- disorganized and shortened by 2 weeks of age and not visible by 3 weeks of age

abnormal retinal photoreceptor layer morphology

abnormal retinal pigment epithelium morphology
- at 10 days of age the apical processes of the retinal pigment epithelium are elongated and some ezrin staining of the basal retinal pigment epithelium is found indicative of a disruption in cell polarity

abnormal rod electrophysiology

retinal degeneration
- although the retina is normal at 10 days of age, by 14 days of age the outer nuclear layer is reduced in thickness with several pyknotic nuclei and the photoreceptor outer segments are disorganized and shortened, and by 3 weeks of age the photoreceptor layer is reduced to one to two layers of cells with outer segments not visible
- at 3 weeks of age the retina has a grainy appearance and by 12 weeks of age this progresses into large white patches distributed across the entire retina
- routine ophthalmoscopic examination of 8 week-old homozygous mice revealed mottling of the retina and atrophy of the retinal vasculature
- standard pathological examination of two mutant miced aged 224 days revealed severe bilateral retinal degeneration
- yer is reduced to one to two layers of cells with outer segments not visible

retinal photoreceptor degeneration

thin retinal outer nuclear layer
- evident by 2 weeks of age and progressing such that by 3 weeks of age the outer nuclear layer is only one to two nuclei in thickness

nervous system phenotype

abnormal photoreceptor outer segment morphology
- disorganized and shortened by 2 weeks of age and not visible by 3 weeks of age

axon degeneration
- standard pathological examination of two mutant mice aged 224 days revealed dystrophic axons in the brainstem and spinal cord

brain vacuoles
- progressive leukoencephalopathy results in vacuoles in the white matter tracts and cerebellum evident by 7 months of age and more severe at 18 months of age although no resulting overt behavioral expression is found

neurodegeneration
- standard pathological examination of two mutant mice aged 224 days revealed status spongiosus of the brain and eosinophilic inclusions in the brainstem and spinal cord

retinal photoreceptor degeneration

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- at 10 days of age the apical processes of the retinal pigment epithelium are elongated and some ezrin staining of the basal retinal pigment epithelium is found indicative of a disruption in cell polarity

reproductive system phenotype

abnormal spermatogenesis

abnormal spermiogenesis
- standard pathological examination of the testes of two mutant mice aged 224 days revealed aspermiogenesis

azoospermia
- by 20 weeks of age homozygotes have only a few spermatogonial stem cells, although Sertoli cells remain
- even as early as 6 weeks of age homozygotes are azoospermic with severe degradation of spermatogenesis and are devoid of spermatocytes, spermatids, and spermatozoa with elongated tails

References

Additional - Clcn2^nmf240 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- black
  Related Genotype: a/a
Citation
When using the C57BL/6J-Clcn2^nmf240/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005095 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 wildtype for Clcn2<nmf240>

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.

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Clcn2nmf240

Allele Symbol: Clcn2nmf240

Disease Terms

Research Areas By Phenotype

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

Genotype: Clcn2nmf240 related

Mammalian Phenotype Terms by Genotype

Genotype: Clcn2nmf240/Clcn2nmf240C57BL/6J-Clcn2/J

cellular phenotype

vision/eye phenotype

nervous system phenotype

pigmentation phenotype

reproductive system phenotype

References

Additional - Clcn2nmf240 related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

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

Clcn2^nmf240

Allele Symbol: Clcn2^nmf240

Genotype: Clcn2^nmf240 related

Genotype: Clcn2^nmf240/Clcn2^nmf240
C57BL/6J-Clcn2/J

Additional - Clcn2^nmf240 related