Overview

Retinal degeneration 8 (rd8) is a spontaneous frame shift mutation in the Crb1 (crumbs homolog 1 (Drosophila)) gene. Mice homozygous for the rd8 allele exhibit a discontinuous and fragmented zona adherens, shortened photoreceptor inner and outer segments, and areas of retinal degeneration (retinal spotting).

Genetic overview

Genetic Background	Generation
	N2N4F?+26 (2020-04-23 00:00:00)

Crb1^rd8

Allele Type	Gene Symbol	Gene Name
Spontaneous	Crb1	crumbs family member 1, photoreceptor morphogenesis associated

Cdh23^ahl

Allele Type	Gene Symbol	Gene Name
Spontaneous	Cdh23	cadherin 23 (otocadherin)

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Research Applications

Neurobiology Research
Sensorineural Research
Developmental Biology Research
Cell Biology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$205.90 Domestic price for female

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Details

Important Note

The C57BL/6J background strain is homozygous for the age related hearing loss mutation Cdh23^ahl, which on this background results in progressive hearing loss with onset after 10 months of age.

Detailed Description

Crb1 (crumbs homolog 1 (Drosophila)) encodes a transmembrane protein that localizes to the apical membrane of epithelial cells and is involved cell polarity in the retina and in the assembly of zonula adherens. Mutations in CRB1 are associated with retinitis pigmentosa and Lebers congenital amaurosis. Mice homozygous for retinal degeneration 8 (rd8) exhibit a discontinuous and fragmented zona adherens, shortened photoreceptor inner and outer segments by 2 weeks of age, and large retinal spots. In contrast to phenotypes associated with other retinal degeneration alleles, retinal degeneration in rd8 mutants is localized to the retinal spots. Within these spots, caused by retinal folds and pseudorosettes, retinal thinning in both the inner and outer nuclear layers is observed. The phenotype associated with rd8 allele is variable depending on genetic background. On the C57BL/6 background, 19% of homozygotes do not exhibit retinal spotting.

Development

Although all C3H strains carry the retinal degeneration 1 mutation of Pde6b, retinas of C3fBAnl.Cg-Cat^b/AnlJ mice were found to have a peculiar, granular appearance distinct from the usual retinal degeneration 1 phenotype. F2 progeny of a cross of C3fBAnl.Cg-Cat^b/AnlJ and C57BL/6ByJ mice exhibited three retinal phenotypes: 1) normal; 2) patches of pigment deposition and large, diffuse pigmented regions typical of retinal degeneration 1 homozygotes; and 3) small, discrete, light-colored dots throughout the fundus. Mice exhibiting the last phenotype were intercrossed among themselves to produce a stock that was homozygous for Mfrp^rd6 and for the wild-type allele of Pde6b. During this process, a separate mutation with a distinct map position was identified and characterized as Crb1^rd8. STOCK Crb1^rd8 Mfrp^rd6/J was homozygous for both Mfrp^rd6 and Crb1^rd8 on this mixed genetic background that derived in part from C57BL/6ByJ, C3H, 101, and a linkage testing stock derived from non-inbred stocks. In order to isolate Crb1^rd8 this stock was backcrossed to C57BL/6ByJ once more, the offspring intercrossed, and their offspring were selected for the Crb1^rd8 phenotype. This mutation was then backcrossed to C57BL/6J for 4 generations before this strain was maintained by sibling intercrossing.

Control Suggestions

C57BL/6J (Stock Number 000664) is only an approximate control for this stock, whose genetic background is ~87.5% C57BL/6J and ~12.5% C3HfB/Ga.

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Mehalow AK; Kameya S; Smith RS; Hawes NL; Denegre JM; Young JA; Bechtold L; Haider NB; Tepass U; Heckenlively JR; Chang B; Naggert JK; Nishina PM. 2003. CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet 12(17):2179-89PubMed: 12915475 MGI: J:85459

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Genetics

Crb1^rd8

Allele Symbol: Crb1^rd8

Allele Name	retinal degeneration 8
Allele Type	Spontaneous
Allele Synonym(s)	Crb1^6N; nmf144; Rd8^-
Gene Symbol and Name	Crb1, crumbs family member 1, photoreceptor morphogenesis associated
Gene Synonym(s)
Strain of Origin	C57BL/6By or C57BL/6N
Chromosome	1
Molecular Note	The mutation in the rd8 mouse has been identified as a single base deletion of a C (G on forward strand) at coding nucleotide 3481 in the gene. This deletion causes a frame shift and a premature stop codon that truncates the transmembrane and cytoplasmic domain of the protein after amino acid 1207. This mutation has been found to be present in all sublines of C57BL/6N and in C57BL/6ByJ, but not in any C57BL/6J subline. It occurred sometime between transfer of mice from JAX to NIH, in 1951, and from NIH to Donald Bailey, in 1961.

Cdh23^ahl

Allele Symbol: Cdh23^ahl

Allele Name	age related hearing loss 1
Allele Type	Spontaneous
Allele Synonym(s)	Cdh23^753A; mdfw
Gene Symbol and Name	Cdh23, cadherin 23 (otocadherin)
Gene Synonym(s)
Strain of Origin	multiple strains
Chromosome	10
Molecular Note	Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G to A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870). This hypomorphic allele changes splice donor site G-GT to A-GT, causing frame skipping of exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Leber congenital amaurosis 8

Research Areas By Phenotype

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

Genotype: Cdh23^ahl related

Neurobiology Research
- Hearing Defects
  - Age related hearing loss
Sensorineural Research
- Hearing Defects
  - Age related hearing loss

Genotype: Crb1^rd8 related

Developmental Biology Research
- Eye Defects
Sensorineural Research
- Retinal Degeneration
Cell Biology Research
- Defects in Cell Adhesion Molecules
Mouse/Human Gene Homologs
- Retinitis pigmentosa 12; Leber congenital amaurosis (CLA)

Mammalian Phenotype Terms by Genotype

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

Genotype: Crb1^rd8/Crb1^rd8
involves: C57BL/6N

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- retinal pigment epithelium vacuolation

vision/eye phenotype

retinal degeneration
- fundus lesions(spots) coalesce to form diffuse lesions or large patches and are visible by histological examination as early as 6 weeks of age
- nonimflammatory retinal degeneration is observed in the inner and outer nuclear layers, the outer plexiform layer and photoreceptor outer segments
- appearance of retinal lesions or spots is variable

abnormal retinal pigment epithelium morphology
- retinal pigment epithelium vacuolation

Genotype: Crb1^rd8/Crb1^rd8
B6.Cg-Crb1 Jak3<+>/Boc

cardiovascular system phenotype

retinal neovascularization

abnormal retinal vasculature morphology

pigmentation phenotype

abnormal retinal pigmentation

abnormal retinal pigment epithelium morphology

vision/eye phenotype

abnormal retinal vasculature morphology

retinal neovascularization

abnormal retinal pigment epithelium morphology

retinal spots

abnormal retinal pigmentation

abnormal retina morphology
- retinal neovascularization with retinal depigmentation spots are found by 1 month of age, a more mild phenotype that that found in mice also homozygous for a point mutation in Janus kinase 3

Genotype: Crb1^rd8/Crb1^rd8
B6.Cg-Crb1

mammalian phenotype

vision/eye phenotype
- Background Sensitivity - mice no longer display the spotting phenotype when backcrossed from a CAST/EiJ background onto a C57BL/6 background

Genotype: Crb1^rd8/Crb1^rd8
involves: C3HfB6/Ga * C57BL/6 * CAST/EiJ

vision/eye phenotype

abnormal retina morphology
- Background Sensitivity - 19% of mice do not display the spotting phenotype on a CAST/EiJ mixed background

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

Genotype: Crb1^rd8/Crb1^rd8
STOCK Crb1/J

vision/eye phenotype

photoreceptor outer segment degeneration
- by week 10 the outer segment begins to fragment
- by 5 months only a few outer segment fragments remain

short photoreceptor outer segment
- the photoreceptor outer segments are shortened

abnormal retina outer limiting membrane morphology
- the external limiting membrane in the retina is fragmented and disorganized at 2 weeks and is more severe at 4 weeks

abnormal photoreceptor inner segment morphology
- the photoreceptor inner segments lose their orderly arrangement
- swelling occurs in portions of the inner segments
- by 5 months the inner segment approaches the retinal pigment epithelium

abnormal retinal photoreceptor morphology
- the photoreceptor lamellae breaks down

abnormal retina morphology
- retinal thinning in both the inner and outer segment is observed

abnormal Muller cell morphology
- Muller cells exhibit increased electron density and cytoplasmic strands that are more easily traced through the plexiform layer than in wild-type mice

abnormal ocular fundus morphology
- mice exhibit large, irregularly shaped spots concentrated in the inferior nasal quadrant of the fundus as early as week 3 that correspond to retinal folds and pseudorosettes

thin retinal outer nuclear layer
- in older mice, the retinal outer nuclear layer is reduced to a single row of nuclei

short photoreceptor inner segment
- at 4 weeks the photoreceptor inner segments are 25% shorter

decreased retinal photoreceptor cell number
- in the region of focal degeneration photoreceptors are lost

nervous system phenotype

photoreceptor outer segment degeneration
- by week 10 the outer segment begins to fragment
- by 5 months only a few outer segment fragments remain

abnormal photoreceptor inner segment morphology
- by 5 months the inner segment approaches the retinal pigment epithelium
- the photoreceptor inner segments lose their orderly arrangement
- swelling occurs in portions of the inner segments

abnormal retinal photoreceptor morphology
- the photoreceptor lamellae breaks down

abnormal Muller cell morphology
- Muller cells exhibit increased electron density and cytoplasmic strands that are more easily traced through the plexiform layer than in wild-type mice

short photoreceptor inner segment
- at 4 weeks the photoreceptor inner segments are 25% shorter

decreased retinal photoreceptor cell number
- in the region of focal degeneration photoreceptors are lost

short photoreceptor outer segment
- the photoreceptor outer segments are shortened

References

Mehalow AK; Kameya S; Smith RS; Hawes NL; Denegre JM; Young JA; Bechtold L; Haider NB; Tepass U; Heckenlively JR; Chang B; Naggert JK; Nishina PM. 2003. CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet 12(17):2179-89PubMed: 12915475 MGI: J:85459

Additional - Cdh23^ahl related

Additional - Crb1^rd8 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Crb1End Point
- Genotyping resources and troubleshooting
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the STOCK Crb1^rd8/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003392 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

MGL277 (M277) (Low)

Pricing & Availability

Availability Varies

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Homozygous for Crb1<rd8>, 1 pair minimum

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

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Crb1rd8

Allele Symbol: Crb1rd8

Cdh23ahl

Allele Symbol: Cdh23ahl

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Cdh23ahl related

Genotype: Crb1rd8 related

Mammalian Phenotype Terms by Genotype

Genotype: Crb1rd8/Crb1rd8involves: C57BL/6N

pigmentation phenotype

vision/eye phenotype

Genotype: Crb1rd8/Crb1rd8B6.Cg-Crb1 Jak3<+>/Boc

cardiovascular system phenotype

pigmentation phenotype

vision/eye phenotype

Genotype: Crb1rd8/Crb1rd8B6.Cg-Crb1

mammalian phenotype

Genotype: Crb1rd8/Crb1rd8involves: C3HfB6/Ga * C57BL/6 * CAST/EiJ

vision/eye phenotype

Genotype: Crb1rd8/Crb1rd8STOCK Crb1/J

vision/eye phenotype

nervous system phenotype

References

Additional - Cdh23ahl related

Additional - Crb1rd8 related

Genotyping Protocols

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Crb1^rd8

Allele Symbol: Crb1^rd8

Cdh23^ahl

Allele Symbol: Cdh23^ahl

Genotype: Cdh23^ahl related

Genotype: Crb1^rd8 related

Genotype: Crb1^rd8/Crb1^rd8
involves: C57BL/6N

Genotype: Crb1^rd8/Crb1^rd8
B6.Cg-Crb1 Jak3<+>/Boc

Genotype: Crb1^rd8/Crb1^rd8
B6.Cg-Crb1

Genotype: Crb1^rd8/Crb1^rd8
involves: C3HfB6/Ga * C57BL/6 * CAST/EiJ

Genotype: Crb1^rd8/Crb1^rd8
STOCK Crb1/J

Additional - Cdh23^ahl related

Additional - Crb1^rd8 related