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 STOCK Gja8Lop10/J    (Changed: 15-DEC-04 ) STOCK Lop10    (Changed: 15-DEC-04 ) Type Mutant Stock; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?pN1 Generation Definitions   Donating Investigator Dr. Bo Chang,   JAX

Appearance
albino, cataract, small eye
Related Genotype: Tyrp1^b/Tyrp1^b Tyr^c/ Tyr^c Gja8^Lop10/Gja8^Lop10

Description
The lens opacity 10 mutation in Gja8 is semidominant. Homozygotes are microphthalmic with foamy cataract of the entire lens apparent when the eyes open at 12 days of age and increasing in opaqueness with age. Bladder cells are found adjacent to the anterior and posterior subcapsular regions of the lens before birth, the lens nucleus begins to liquefy by 4 days of age and ruptures posteriorly, then the lens capsule thickens. Gja8^Lop10 Heterozygotes are not microphthalmic and the phenotype associated with the mutation varies according to the genetic background. A nuclear haze or snowflake nuclear opacity is found in F1 heterozygotes of some backgrounds while a more severe dense nuclear opacity is evident by 4 weeks of age in F1 heterozygotes of other backgrounds including AKR/J and BALB/cJ. Mice homozygous for the Gja8^tm1Paul targeted mutation, a recessive mutation in which the entire coding region is removed, do not display posterior lens rupture. Additionally, there is a decrease in phosphorylated Gja3 in lens extracts from Gja8^Lop10 homozygotes and mice doubly homozygous for Gja8^Lop10 and a targeted mutation disrupting Gja3 have a less severe phenotype than that of Gja8^Lop10 homozygotes. (Runge et al., 1992; Chang et al., 2002.)

Development
The Gja8^Lop10 mutation arose spontaneously in the offspring of a BALB/cJ x AKR/J cross at The Jackson Laboratory. It was backcrossed three times to BALB/cJ then maintained by sibling mating for many years before cryopreservation of sperm.

Control Information

	Control
	000651 BALB/cJ	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Gja8^Lop10/Gja8⁺

        C;AK-Gja8^Lop10/J

• vision/eye phenotype
• nuclear cataracts
  • fetal nuclear cataract with background dependent variability in expressivity, with dense nuclear opacity at 4 weeks of age on the BALB/cJ and AKR/J mixed background; a less severe phenotype of snowflake opacity with a later onset of 3 months of age is found when outcrossed to some other genetic backgrounds, particularly those of the C57BL group   (MGI Ref ID J:4160)

Gja8^Lop10/Gja8^Lop10

        C;AK-Gja8^Lop10/J

• vision/eye phenotype
• abnormal lens development
  • at 3 weeks of age the lens has only only small gap junction plaques   (MGI Ref ID J:75387)
• abnormal lens fiber morphology
  • although the secondary fibers of the bow region defferentiate normally, the fibers in the deeper regions are severely disrupted by one day of age   (MGI Ref ID J:75387)
• cataracts   (MGI Ref ID J:75387)
  • at 1 day of age small bladder cells are found axially adjacent to the posterior lens capsule, which is of normal thickness, by 2 days of age bladder cells are found adjacent to both the anterior and posterior axial subcapsular regions, and by 4 days of age the lens nucleus begins to liquify and the lens contents begin to displace posteriorly; by 11 days of age the lens capsule has a marked thickening with the lens contents herniated posteriorly, and when the eyes open at 12 days of age lens opacity is evident   (MGI Ref ID J:4160)
• microphthalmia   (MGI Ref ID J:4160)
• ruptured lens capsule   (MGI Ref ID J:75387)

View Research Applications

Research Applications

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

Gja8^Lop10 related

Developmental Biology Research
Eye Defects

Sensorineural Research
Cataracts
      lens extrusion
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gja8Lop10
Allele Name		lens opacity 10
Allele Type		Spontaneous
Common Name(s)		G22R; Lop10;
Strain of Origin		BALB/cJ x AKR/J
Gene Symbol and Name		Gja8, gap junction protein, alpha 8
Chromosome		3
Gene Common Name(s)		Aey5; CAE; CAE1; CX50; CZP1; Cnx50; Lop10; MP70; alpha 8 connexin; connexin 50; lens opacity 10;
General Note		In homozygous mutant mice, eyes are microphthalmic, with a dense white cataract present when eyelids opened at the age of 12 days. Histologic changes could be traced back to the 18th day of gestation. Liquefaction of lens contents had begun by 4 days of age, with posterior herniation by 11 days old. Expression in heterozygotes varied with age and with strain of origin (J:4160).
Molecular Note		The mutation in the lens opacity 10 mouse was identifed as a G-to-C missense mutation in the gene, which is predicted to cause a glycine to arginine substitution at codon 22 of the encoded protein. [MGI Ref ID J:75387]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Chang B; Wang X; Hawes NL; Ojakian R; Davisson MT; Lo WK; Gong X. 2002. A Gja8 (Cx50) point mutation causes an alteration of alpha3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice. Hum Mol Genet 11(5):507-13. [PubMed: 11875045]  [MGI Ref ID J:75387]

Gja8^Lop10 related

Chang B; Hawes NL; Hurd RE; Wang J; Howell D; Davisson MT; Roderick TH; Nusinowitz S; Heckenlively JR. 2005. Mouse models of ocular diseases. Vis Neurosci 22(5):587-93. [PubMed: 16332269]  [MGI Ref ID J:156373]

Chang B; Wang X; Hawes NL; Ojakian R; Davisson MT; Lo WK; Gong X. 2002. A Gja8 (Cx50) point mutation causes an alteration of alpha3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice. Hum Mol Genet 11(5):507-13. [PubMed: 11875045]  [MGI Ref ID J:75387]

Runge PE; Hawes NL; Heckenlively JR; Langley SH; Roderick TH. 1992. Autosomal dominant mouse cataract (Lop-10). Consistent differences of expression in heterozygotes. Invest Ophthalmol Vis Sci 33(11):3202-8. [PubMed: 1399425]  [MGI Ref ID J:4160]

Xia CH; Cheung D; Derosa AM; Chang B; Lo WK; White TW; Gong X. 2006. Knock-in of {alpha}3 connexin prevents severe cataracts caused by an {alpha}8 point mutation. J Cell Sci 119(Pt 10):2138-44. [PubMed: 16687738]  [MGI Ref ID J:108927]

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.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Eye Mutant Resource within the Mouse Mutant Resource collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000651 BALB/cJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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