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Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):E7131-E7139. doi: 10.1073/pnas.1705848114. Epub 2017 Aug 4.

Genetic background-dependent role of Egr1 for eyelid development.

Author information

1
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
2
Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
3
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
4
Pathology Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
5
Pathology/Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick, MD 21702.
6
Department of Medical Genetics, University of Alberta, Edmonton AB, Canada T6G 2H7.
7
Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
8
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; wjl@helix.nih.gov chanc@nei.nih.gov.
9
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; wjl@helix.nih.gov chanc@nei.nih.gov.

Abstract

EGR1 is an early growth response zinc finger transcription factor with broad actions, including in differentiation, mitogenesis, tumor suppression, and neuronal plasticity. Here we demonstrate that Egr1-/- mice on the C57BL/6 background have normal eyelid development, but back-crossing to BALB/c background for four or five generations resulted in defective eyelid development by day E15.5, at which time EGR1 was expressed in eyelids of WT mice. Defective eyelid formation correlated with profound ocular anomalies evident by postnatal days 1-4, including severe cryptophthalmos, microphthalmia or anophthalmia, retinal dysplasia, keratitis, corneal neovascularization, cataracts, and calcification. The BALB/c albino phenotype-associated Tyrc tyrosinase mutation appeared to contribute to the phenotype, because crossing the independent Tyrc-2J allele to Egr1-/- C57BL/6 mice also produced ocular abnormalities, albeit less severe than those in Egr1-/- BALB/c mice. Thus EGR1, in a genetic background-dependent manner, plays a critical role in mammalian eyelid development and closure, with subsequent impact on ocular integrity.

KEYWORDS:

Egr1; eyelid development; genetic background-specific effects; ocular abnormalities; tyrosinase

PMID:
28778995
PMCID:
PMC5576810
DOI:
10.1073/pnas.1705848114
[Indexed for MEDLINE]
Free PMC Article

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