May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Identification of a Major QTL, Which Modifies the Schisis and Layer Disorganization Phenotypes in Rs1htmgc1 Mice
Author Affiliations & Notes
  • B. A. Johnson
    Medical Genetics, Univ of Wisconsin-Madison, Madison, Wisconsin
  • S. Ikeda
    Medical Genetics, Univ of Wisconsin-Madison, Madison, Wisconsin
  • A. Ikeda
    Medical Genetics, Univ of Wisconsin-Madison, Madison, Wisconsin
  • Footnotes
    Commercial Relationships B.A. Johnson, None; S. Ikeda, None; A. Ikeda, None.
  • Footnotes
    Support The Rebecca Meyer Brown Pilot Project Award, Individual Investigator Grant Award from the FFB, NIH Grant R01EY016394, Predoctoral Training Program in Genetics NIH 5T32GM07133
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3000. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      B. A. Johnson, S. Ikeda, A. Ikeda; Identification of a Major QTL, Which Modifies the Schisis and Layer Disorganization Phenotypes in Rs1htmgc1 Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3000.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose:: X-Linked Retinoschisis (XLRS) is a leading cause of inherited juvenile macular degeneration, which is characterized by a splitting of the retina (schisis), loss in central vision, and loss in the ERG b-wave. We study the Rs1htmgc1 mouse, which contains a splice site mutation that is similar to some mutations in human XLRS patients, as a model for XLRS. We noted a broad range of phenotypic severity in a mixed genetic background, which suggested the existence of genetic modifiers. The purpose of this study was to test whether the phenotypic variability is genetically based and to identify the loci underlying this variability.

Methods:: To map the genetic modifiers, we performed a whole genome wide scan using affected animals from an F2 intercross between Rs1htmgc1 and AKR/J mice. All F2 affected animals were phenotyped by histological analysis. Affected animals were scored for the degree of schisis, abnormal layer formation involving the ONL, and the existence of ectopic nuclei between the ONL and the RPE. Each mouse was given a phenotypic score between 0.5 and 3 depending on the severity of the phenotype. All genotypic and phenotypic information was analyzed by QTL Map Manager software version QTXb20.

Results:: We have identified one major QTL on chromosome 7 (F-score=113.3, LOD score= 24.6, p<1x10-6). The AKR/J allele reduced the phenotypic severity of schisis and layer disorganization in a recessive fashion. This QTL is responsible for 46% of the phenotypic variance observed in this intercross, which suggests that a major locus is affecting the phenotypes. We named this QTL Mor1 for modifier of retinoschisis 1. Several candidate genes that are known to be involved in cell adhesion lie within the Mor1 minimal genetic region.

Conclusions:: The morphological phenotypes in Rs1htmgc1 mice are genetically modified by a major locus (Mor1) on chromosome 7, which may be involved in cell adhesion. Identification of the Mor1 gene should provide insight into the molecular mechanism of Rs1h mediated cell adhesion.

Keywords: gene modifiers • gene mapping • retinal adhesion 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.