Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6;129-Crxtm1Clc/J    (Changed: 15-MAY-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?pN1 Generation Definitions   Donating Investigator Connie Cepko,   Harvard Medical School, HHMI

Description
Homozygotes are viable and fertile and do not display any gross physical abnormalities. These mice do not elaborate photoreceptor outer segments and synaptic termini, and they lack cone and rod activities as assayed by electroretinograms. Circadian entrainment activity is attenuated. Protein is not produced as determined by RT-PCR of retinal RNA extracts. This strain may be useful as a model of retinophathy (e.g., Leber's congenital amaurosis (LCA), cone-rod dystrophy-2 (adCRD2), retinitis pigmentosa (RP)), or circadian rhythm modification.

Development
A targeting vector was designed to replace exon 3 and a portion of exon 4 with a PGK-Neo cassette in reverse orientation. The vector was electroporated into a 129S2/SvEvTac-derived TC-1 embryonic stem (ES) cell line. Correctly-targeted ES cells were microinjected into C57BL/6 blastocysts. Resultant chimeric foundation mice were backcrossed to C57BL/6 at least 10 times.

Related Strains

Strains carrying other alleles of Crx

007066

B6.SJL-Tg(Crx-GFP,-ALPP)1Clc/J

View Strains carrying other alleles of Crx     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Leber Congenital Amaurosis 7; LCA7 5

5 Conditionally targeted allele(s)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Crx^tm1Clc/Crx⁺

        involves: 129S6/SvEvTac

• vision/eye phenotype
• abnormal retina morphology
  • although abnormalities are seen at earlier ages, the retina is normal by 3 months of age   (MGI Ref ID J:58796)
• • abnormal photoreceptor outer segment morphology
    • shorter at 2 weeks of age but normal at 3 weeks   (MGI Ref ID J:58796)
  • thin retinal outer nuclear layer
    • 8-10 rows of nuclei at 2 months of age as compared to 14-16 in controls   (MGI Ref ID J:58796)
• nervous system phenotype
• abnormal photoreceptor outer segment morphology
  • shorter at 2 weeks of age but normal at 3 weeks   (MGI Ref ID J:58796)

Crx^tm1Clc/Crx^tm1Clc

        involves: 129S6/SvEvTac

• vision/eye phenotype
• abnormal eye electrophysiology   (MGI Ref ID J:58796)
• • abnormal cone electrophysiology
    • no electroretinogram activity at 1 month of age   (MGI Ref ID J:58796)
    • greater than 90% reduction in activity   (MGI Ref ID J:58796)
  • abnormal rod electrophysiology
    • less than 1% of normal rod activity at 1 month of age   (MGI Ref ID J:58796)
    • "a" and "b" waves in electroretinogram are absent   (MGI Ref ID J:58796)
• abnormal retina morphology   (MGI Ref ID J:58796)
• • abnormal horizontal cell morphology
    • increased concentration and size of horizontal cell neurites which originate from axons   (MGI Ref ID J:88825)
  • abnormal retinal bipolar cell morphology   (MGI Ref ID J:88825)
  • • abnormal retinal cone bipolar cell morphology
      • dendritic trees begin retracting around 5 months   (MGI Ref ID J:88825)
      • axons remain normal   (MGI Ref ID J:88825)
    • abnormal retinal rod bipolar cell morphology
      • very small in size relative to controls at 7 months of age   (MGI Ref ID J:88825)
      • distinctly smaller axons at 1 to 3 months of age   (MGI Ref ID J:88825)
      • dendritic arborization is retracted from outer plexiform layer at 1 to 3 months of age and almost completely retracted by 7 months   (MGI Ref ID J:88825)
  • abnormal retinal outer plexiform layer morphology
    • photoreceptor terminals are highly disorganized with no well formed rod spherules or cone pedicles   (MGI Ref ID J:95886)
  • abnormal retinal photoreceptor layer morphology   (MGI Ref ID J:58796)
  • • abnormal retinal photoreceptor morphology
      • photoreceptor cells dislocated to just beneath pigment epithelium   (MGI Ref ID J:58796)
    • • abnormal photoreceptor inner segment morphology
        • very rarely do connecting cilia emerge from the inner segment by 7 days of age   (MGI Ref ID J:95886)
        • connecting cilia are unusually long at later stages   (MGI Ref ID J:95886)
      • abnormal photoreceptor outer segment morphology
        • numerous small vesicles are present, possibly derived from the inner segment   (MGI Ref ID J:95886)
        • abnormal structures occasionally seen attached to connecting cilia may be malformed outer segments   (MGI Ref ID J:95886)
      • • absent photoreceptor outer segment
          • at 2 to 3 weeks of age   (MGI Ref ID J:58796)
  • thin retinal outer nuclear layer
    • thin at 3 weeks of age   (MGI Ref ID J:58796)
    • 1-3 rows of nuclei at 6 months of age   (MGI Ref ID J:58796)
    • 12 rows at 1 month of age   (MGI Ref ID J:88825)
    • only 1 row centrally at 7 months of age but 2 rows more peripherally   (MGI Ref ID J:88825)
• behavior/neurological phenotype
• abnormal circadian rhythm
  • although mice continue to be predominantly dark active, dark cycle activity is reduced   (MGI Ref ID J:58796)
• • delayed circadian phase
    • photoentrainment is slower than in controls after a 4 hour advance in the light-dark cycle   (MGI Ref ID J:58796)
• nervous system phenotype
• abnormal horizontal cell morphology
  • increased concentration and size of horizontal cell neurites which originate from axons   (MGI Ref ID J:88825)
• abnormal retinal bipolar cell morphology   (MGI Ref ID J:88825)
• • abnormal retinal cone bipolar cell morphology
    • dendritic trees begin retracting around 5 months   (MGI Ref ID J:88825)
    • axons remain normal   (MGI Ref ID J:88825)
  • abnormal retinal rod bipolar cell morphology
    • very small in size relative to controls at 7 months of age   (MGI Ref ID J:88825)
    • distinctly smaller axons at 1 to 3 months of age   (MGI Ref ID J:88825)
    • dendritic arborization is retracted from outer plexiform layer at 1 to 3 months of age and almost completely retracted by 7 months   (MGI Ref ID J:88825)
• abnormal retinal photoreceptor morphology
  • photoreceptor cells dislocated to just beneath pigment epithelium   (MGI Ref ID J:58796)
• • abnormal photoreceptor inner segment morphology
    • very rarely do connecting cilia emerge from the inner segment by 7 days of age   (MGI Ref ID J:95886)
    • connecting cilia are unusually long at later stages   (MGI Ref ID J:95886)
  • abnormal photoreceptor outer segment morphology
    • numerous small vesicles are present, possibly derived from the inner segment   (MGI Ref ID J:95886)
    • abnormal structures occasionally seen attached to connecting cilia may be malformed outer segments   (MGI Ref ID J:95886)
  • • absent photoreceptor outer segment
      • at 2 to 3 weeks of age   (MGI Ref ID J:58796)

View Research Applications

Research Applications

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

Neurobiology Research
Circadian Rhythms

Sensorineural Research
Eye Defects
Retinal Degeneration
      retinitis pigmentosa

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Crxtm1Clc
Allele Name		targeted mutation 1, Constance L Cepko
Allele Type		Targeted (knock-out)
Common Name(s)		Crx-;
Mutation Made By		Connie Cepko,   Harvard Medical School, HHMI
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC1/TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Crx, cone-rod homeobox containing gene
Chromosome		7
Gene Common Name(s)		CORD2; CRD; Crx1; LCA7; OTX3;
Molecular Note		The homeodomain coding region containing exon 3 and a portion of exon 4 was replaced by a neomycin selection cassette. RT-PCR analysis showed an absence of transcript in the retinas of homozygous mutant mice. [MGI Ref ID J:58796]

Genotyping

Genotyping Information

Genotyping Protocols

Crx^tm1Clc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Furukawa T; Morrow EM; Li T; Davis FC; Cepko CL. 1999. Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Nat Genet 23(4):466-70. [PubMed: 10581037]  [MGI Ref ID J:58796]

Additional References

Crx^tm1Clc related

Blackshaw S; Fraioli RE; Furukawa T; Cepko CL. 2001. Comprehensive analysis of photoreceptor gene expression and the identification of candidate retinal disease genes. Cell 107(5):579-89. [PubMed: 11733058]  [MGI Ref ID J:94901]

Goldshmit Y; Galley S; Foo D; Sernagor E; Bourne JA. 2010. Anatomical changes in the primary visual cortex of the congenitally blind Crx-/- mouse. Neuroscience 166(3):886-98. [PubMed: 20034544]  [MGI Ref ID J:159739]

Kaneko H; Dridi S; Tarallo V; Gelfand BD; Fowler BJ; Cho WG; Kleinman ME; Ponicsan SL; Hauswirth WW; Chiodo VA; Kariko K; Yoo JW; Lee DK; Hadziahmetovic M; Song Y; Misra S; Chaudhuri G; Buaas FW; Braun RE; Hinton DR; Zhang Q; Grossniklaus HE; Provis JM; Madigan MC; Milam AH; Justice NL; Albuquerque RJ; Blandford AD; Bogdanovich S; Hirano Y; Witta J; Fuchs E; Littman DR; Ambati BK; Rudin CM; Chong MM; Provost P; Kugel JF; Goodrich JA; Dunaief JL; Baffi JZ; Ambati J. 2011. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471(7338):325-30. [PubMed: 21297615]  [MGI Ref ID J:170350]

Kim DS; Matsuda T; Cepko CL. 2008. A core paired-type and POU homeodomain-containing transcription factor program drives retinal bipolar cell gene expression. J Neurosci 28(31):7748-64. [PubMed: 18667607]  [MGI Ref ID J:139494]

Koike C; Nishida A; Ueno S; Saito H; Sanuki R; Sato S; Furukawa A; Aizawa S; Matsuo I; Suzuki N; Kondo M; Furukawa T. 2007. Functional roles of Otx2 transcription factor in postnatal mouse retinal development. Mol Cell Biol 27(23):8318-29. [PubMed: 17908793]  [MGI Ref ID J:128994]

Livesey FJ; Furukawa T; Steffen MA; Church GM; Cepko CL. 2000. Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx. Curr Biol 10(6):301-10. [PubMed: 10744971]  [MGI Ref ID J:61126]

Morrow EM; Furukawa T; Raviola E; Cepko CL. 2005. Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice. BMC Neurosci 6(1):5. [PubMed: 15676071]  [MGI Ref ID J:95886]

Omori Y; Katoh K; Sato S; Muranishi Y; Chaya T; Onishi A; Minami T; Fujikado T; Furukawa T. 2011. Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the otx2-deficient retina. PLoS One 6(5):e19685. [PubMed: 21602925]  [MGI Ref ID J:172744]

Onishi A; Peng GH; Hsu C; Alexis U; Chen S; Blackshaw S. 2009. Pias3-dependent SUMOylation directs rod photoreceptor development. Neuron 61(2):234-46. [PubMed: 19186166]  [MGI Ref ID J:147163]

Peng GH; Chen S. 2011. Active opsin loci adopt intrachromosomal loops that depend on the photoreceptor transcription factor network. Proc Natl Acad Sci U S A 108(43):17821-6. [PubMed: 22006320]  [MGI Ref ID J:177494]

Peng GH; Chen S. 2007. Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation. Hum Mol Genet 16(20):3433-52. [PubMed: 17656371]  [MGI Ref ID J:129889]

Pignatelli V; Cepko CL; Strettoi E. 2004. Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis. J Comp Neurol 469(3):351-9. [PubMed: 14730587]  [MGI Ref ID J:88825]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

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• This strain is included in the Induced Mutant Resource Colony collection.

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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.

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