Description

Strain Information

Former Names A.BY-H2b H2-T18b/SnJ-Dstncorn1/J    (Changed: 15-DEC-04 ) A.BY-H2b H2-T18b/SnJ-corn1    (Changed: 15-DEC-04 ) A.BY/SnJ-corn1    (Changed: 15-DEC-04 ) Type Congenic; Major Histocompatibility Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse

Appearance
albino, vascularized cornea, cataract
Related Genotype: a/a Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Dstn^corn1/Dstn^corn1

Description
Mice homozygous for the recessive Dstn^corn1 mutation have abnormally proliferative basal corneal epithelial cells. Focal areas of corneal epithelial hyperplasia are found by one week of age, and neovascularization is found by 14 days of age when the eyes open. This neovascularization, which progresses during the first two months of age, is not found in mice homozygous for the Dstn^corn-2J allele (which is a point mutation leading to a change in a single amino acid residue). In both mutants the corneal epithelial cells show increased levels and altered organizational pattern of filamentous actin. The areas of thickened cortical epithelia yield a roughened, opaque corneal surface.

At 4 weeks of age in Dstn^corn1 homozygotes, expression of keratin 14 and involucrin extend into the suprabasal layer in the areas of hyperplastic corneal epithelia. There is also an increase in the levels of expression of cofilin 1, lumican and keratocan with lumican showing abnormal expression in epithelial cells. (Smith et al., 1996; Wang et al., 2001; Ikeda et al., 2003.) Homozygotes develop hemangiogenesis at 4 weeks of age; onset of lymphangiogenesis is delayed, less intense and regresses earlier compared with hemangiogenesis. (Cursiefen et al., 2005).

Control Information

	Control
	000646 A/J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Dstn^corn1/Dstn^corn1

        A.By-H2^b/SnJ

• vision/eye phenotype
• abnormal corneal epithelium morphology (MGI Ref ID J:114973)
  • focal areas ~1 mm in diameter are elevated above corneal surface
  • epithelium has "dry", white appearance
  • at 12 days of age, mice show mild edema of basal epithelial layers and corneal surface shows irregularities with focal areas ~1 mm in diameter elevated above corneal surface; corneal surface is increasingly roughened and irregular, until 70 days of age when irregularity stabilizes
  • at 21 and 30 days of age, thickening of epithelium increases
  • surface epithelial cell nuclei are pyknotic and cytoplasm has granular appearance
  • eosinophilia is seen in superficial epithelial cells at 12 days of age, but is decreased by 60 days of age
  • at 4 weeks of age the hyperplastic corneal epithelium has altered expression of keratin 14, involucrin, and lumican
• cataracts (MGI Ref ID J:31798)
  • bilateral cataracts develop by 45-50 days of age; progressive lenticular opacification is observed to 8 months of age
  • cataracts are manifested by liquefaction of lens fibers and posterior migration of lens epithelial nuclei
• corneal vascularization (MGI Ref ID J:98465)
  • mice exhibit spontaneous corneal vascularization
  • corneal injection of sflt-1 (secreted isoform of the cell surface receptor membrane-bound Flt1) protein reduces the area of vascularization compared to untreated mutants
  • neovascularization is present in limbus at E18; vascularization grows and reaches center of cornea at 45 days
• cellular phenotype
• increased cell proliferation (MGI Ref ID J:31798)
  • in homozygotes, there are 10-fold more proliferating corneal epithelial cells than in wild-type or heterozygous mice
• cardiovascular system phenotype
• increased angiogenesis (MGI Ref ID J:98465)
  • in the cornea
• pathological neovascularization (MGI Ref ID J:98465)
  • hemangiogenesis in the normally avascular cornea is first seen as single sprouts around 2 weeks of age, by 3 weeks of age slit-lamp examination shows outgrowth of limbal blood vessels, and blood vessels cover the corneal surface by approximately 6 weeks of age.
  • corneal hemangiogenesis precedes lymphangiogenesis by approximately one week, and there is no corneal blood vessel regression in the first year.
  • Corneal hemangiogenesis and lymphangiogenesis can be inhibited by treatment with an antibody blocking vascular enothelial growht factor receptor 3
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:98465)
  • the aqueous humor has a normal protein and leukocyte count indicating that the corneal neovascularization and lymphangiogenesis are not mediated primarily by inflammation
• lymphangiogenesis (MGI Ref ID J:98465)
  • Corneal lymphangiogenesis begins with small sprouts around 3 weeks of age, a week after corneal hemangiogenesis begins, and lymphatic vessels are clearly visible by 4 to 6 weeks of age. Vessel fragmentation is seen as early as 2 months of age. Thus, corneal lymphangiogenesis is less severe than hemangiogenesis and comparatively delayed.
  • This corneal lymphangiogenesis occurs in a low inflammatory context in which there are only slightly more CD45 positive cells at 4 weeks of age than in controls.

View Research Applications

Research Applications

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

Dstn^corn1 related

Cancer Research
Other (tumor metastasis)

Cardiovascular Research
Vascular Defects

Cell Biology Research
Cell Cycle Regulation
Genes Regulating Growth and Proliferation
Post-translational Processing
Signal Transduction

Developmental Biology Research
Eye Defects

Sensorineural Research
Cataracts (cortical)
Eye Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Dstncorn1
Allele Name		corneal disease 1
Allele Type		Spontaneous
Common Name(s)		corn1;
Strain of Origin		A.By-H2/SnJ
Gene Symbol and Name		Dstn, destrin
Chromosome		2
Gene Common Name(s)		2610043P17Rik; ACTDP; ADF; AU042046; RIKEN cDNA 2610043P17 gene; bA462D18.2; corn1; corneal disease 1; expressed sequence AU042046; sid23p;
Molecular Note		The mutation in the corn1 mouse was identified as a 35 kb deletion encompassing the entire coding region of the gene. [MGI Ref ID J:83125]
Gene Symbol and Name		H2-T18, histocompatibility 2, T region locus 18
Chromosome		17
Gene Common Name(s)		H-2T18; TL Ag; Tla; thymus leukemia antigen;
Gene Symbol and Name		H2, histocompatibility-2, MHC
Chromosome		17
Gene Common Name(s)		H-2; MHC-II;

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Ikeda S; Cunningham LA; Boggess D; Hobson CD; Sundberg JP; Naggert JK; Smith RS; Nishina PM. 2003. Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Hum Mol Genet 12(9):1029-37. [PubMed: 12700171]  [MGI Ref ID J:83125]

Wang I; Kao CW; Liu C; Saika S; Nishina PM; Sundberg JP; Smith RS; Kao WW. 2001. Characterization of Corn1 mice: Alteration of epithelial and stromal cell gene expression. Mol Vis 7:20-6. [PubMed: 11182022]  [MGI Ref ID J:83043]

Dstn^corn1 related

Ambati BK; Nozaki M; Singh N; Takeda A; Jani PD; Suthar T; Albuquerque RJ; Richter E; Sakurai E; Newcomb MT; Kleinman ME; Caldwell RB; Lin Q; Ogura Y; Orecchia A; Samuelson DA; Agnew DW; St Leger J; Green WR; Mahasreshti PJ; Curiel DT; Kwan D; Marsh H; Ikeda S; Leiper LJ; Collinson JM; Bogdanovich S; Khurana TS; Shibuya M; Baldwin ME; Ferrara N; Gerber HP; De Falco S; Witta J; Baffi JZ; Raisler BJ; Ambati J. 2006. Corneal avascularity is due to soluble VEGF receptor-1. Nature 443(7114):993-7. [PubMed: 17051153]  [MGI Ref ID J:114973]

Cursiefen C; Ikeda S; Nishina PM; Smith RS; Ikeda A; Jackson D; Mo JS; Chen L; Dana MR; Pytowski B; Kruse FE; Streilein JW. 2005. Spontaneous Corneal Hem- and Lymphangiogenesis in Mice with Destrin-Mutation Depend on VEGFR3 Signaling. Am J Pathol 166(5):1367-77. [PubMed: 15855638]  [MGI Ref ID J:98465]

Ikeda S; Cunningham LA; Boggess D; Hobson CD; Sundberg JP; Naggert JK; Smith RS; Nishina PM. 2003. Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Hum Mol Genet 12(9):1029-37. [PubMed: 12700171]  [MGI Ref ID J:83125]

Kousaka K; Kiyonari H; Oshima N; Nagafuchi A; Shima Y; Chisaka O; Uemura T. 2008. Slingshot-3 dephosphorylates ADF/cofilin but is dispensable for mouse development. Genesis 46(5):246-55. [PubMed: 18442045]  [MGI Ref ID J:136245]

Smith RS; Hawes NL; Kuhlmann SD; Heckenlively JR; Chang B; Roderick TH; Sundberg JP. 1996. Corn1: a mouse model for corneal surface disease and neovascularization. Invest Ophthalmol Vis Sci 37(2):397-404. [PubMed: 8603845]  [MGI Ref ID J:31798]

Verdoni AM; Smith RS; Ikeda A; Ikeda S. 2008. Defects in actin dynamics lead to an autoinflammatory condition through the upregulation of CXCL5. PLoS ONE 3(7):e2701. [PubMed: 18628996]  [MGI Ref ID J:139239]

Wang I; Kao CW; Liu C; Saika S; Nishina PM; Sundberg JP; Smith RS; Kao WW. 2001. Characterization of Corn1 mice: Alteration of epithelial and stromal cell gene expression. Mol Vis 7:20-6. [PubMed: 11182022]  [MGI Ref ID J:83043]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Eye Mutant Resource within the Mouse Mutant Resource collection.

Control Information

	Control
	000646 A/J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

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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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