September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Mfrp regulates ocular growth in mice and interacts with Prss56
Author Affiliations & Notes
  • Mark P Krebs
    The Jackson Laboratory, Bar Harbor, Maine, United States
  • Wanda Hicks
    The Jackson Laboratory, Bar Harbor, Maine, United States
  • Patsy M Nishina
    The Jackson Laboratory, Bar Harbor, Maine, United States
  • Footnotes
    Commercial Relationships   Mark Krebs, None; Wanda Hicks, None; Patsy Nishina, None
  • Footnotes
    Support  NIH Grants EY011996, P30CA034196
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3609. doi:
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      Mark P Krebs, Wanda Hicks, Patsy M Nishina; Mfrp regulates ocular growth in mice and interacts with Prss56. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3609.

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

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Abstract

Purpose : Variations in the genes encoding membrane-frizzled related protein (MFRP) and a secreted serine protease (PRSS56) cause posterior microphthalmia and nanophthalmia in human patients, implicating these genes in the control of ocular growth. Although Mfrp and Prss56 mutant mice have been described, so far only Prss56 mutant mice have been reported with decreased axial length. Moreover, whether Mfrp and Prss56 function in the same or different genetic networks is unknown. The purpose of this study is to test whether ocular growth is affected by Mfrp mutation in mutant mice, and whether Mfrp and Prss56 interact genetically in the control of axial length.

Methods : Inbred homozygous Mfrprd6 and Prss56glcr4 mice on the C57BL/6J (B6J) background were bred separately or intercrossed to yield heterozygous or wild-type controls or singly and doubly homozygous mutant mice. Mice were examined from 0.6 to 8 months of age by optical coherence tomography (OCT) B-scans and rectangular volumes. Changes in ocular axial length and retinal folds were assessed by image analysis in ImageJ/Fiji. Student’s t-test and one-way ANOVA with Tukey post-hoc comparisons were used for statistical analyses.

Results : Axial length in homozygous Mfrprd6 mice was unchanged compared to control mice at 0.6 and 2 months of age (N=2-7, P>0.6), but was significantly lower at 3 and 8 months of age (N=2-9, P<0.01). Additionally, ANOVA analysis at 8 months of age (N=4-9) indicated significant effects of strain on axial length when singly and doubly mutant mice and controls were analyzed (F(3,23) = 35.4, P<0.0001). Post-hoc tests indicated a significant decrease in axial length by 4-5% when these mutant mice were compared to controls (P<0.0001), but no significant differences when compared to each other (P>0.25). Retinal folds found in older Prss56glcr4 mice were absent from doubly homozygous mice.

Conclusions : The reduced ocular axial length of Mfrprd6 mice supports the hypothesis that Mfrp controls eye growth in mice, as well as humans, and suggests that these mice are suitable as a model of MFRP microphthalmia. The absence of an additive effect on axial length in doubly homozygous Mfrp and Prss56 mutant mice suggests that the two genes interact in the same growth pathway, as previously inferred from the upregulation of Prss56 mRNA levels in Mfrprd6 eyes. Interaction of the genes is also indicated by the loss of retinal folds in doubly homozygous mutants.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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