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Varied manifestations of persistent hyperplastic primary vitreous with graded somatic mosaic deletion of a single gene. Mol Vis 2014;20:215-30



Pubmed ID


Pubmed Central ID


Scopus ID

2-s2.0-84896807326 (requires institutional sign-in at Scopus site)   3 Citations


PURPOSE: Persistent hyperplastic primary vitreous (PHPV) represents a developmental eye disease known to have diverse manifestations ranging from a trivial remnant of hyaloid vessels to a dense fibrovascular mass causing lens opacity and retinal detachment. PHPV can be modeled in mice lacking individual genes, but certain features of such models differ from the clinical realm. For example, mice lacking the Arf gene have uniformly severe disease with consistent autosomal recessive disease penetrance. We tested whether the graded somatic loss of Arf in a subset of cells in chimeric mice mimics the range of disease in a non-heritable manner.

METHODS: Wild type ↔ Arf(-/-) mouse chimeras were generated by morulae fusion, and when the mice were 10 weeks old, fundoscopic, slit-lamp, and histological evaluations were performed. The relative fraction of cells of the Arf(-/-) lineage was assessed with visual, molecular genetic, and histological analysis. Objective quantification of various aspects of the phenotype was correlated with the genotype.

RESULTS: Sixteen chimeras were generated and shown to have low, medium, and high contributions of Arf(-/-) cells to tail DNA, the cornea, and the retinal pigment epithelium (RPE), with excellent correlation between chimerism in the tail DNA and the RPE. Phenotypic differences (coat color and severity of eye disease) were evident, objectively quantified, and found to correlate with the contribution of Arf(-/-) cells to the RPE and tail-derived DNA, but not the cornea.

CONCLUSIONS: Generating animals composed of different numbers of Arf(-/-) cells mimicked the range of disease severity observed in patients with PHPV. This establishes the potential for full manifestations of PHPV to be caused by somatic mutations of a single gene during development.

Author List

Mary-Sinclair MN, Wang X, Swanson DJ, Sung CY, Mendonca EA, Wroblewski K, Baumer SH, Goldowitz D, Jablonski MM, Skapek SX


Shannon H. Baumer-Mouradian MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Lineage
Cyclin-Dependent Kinase Inhibitor p19
Gene Deletion
Mice, Inbred C57BL
Persistent Hyperplastic Primary Vitreous
Retinal Pigment Epithelium