Genetic background-dependent role of Egr1 for eyelid development

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 Tyr c tyrosinase mutation appeared to contribute to the phenotype, because crossing the independent Tyr c-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 backgrounddependent manner, plays a critical role in mammalian eyelid development and closure, with subsequent impact on ocular integrity.Egr1 | eyelid development | ocular abnormalities | tyrosinase | genetic background-specific effects

New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy—Beyond Classical Gene Candidates

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Tyr is Responsible for the Cctq1a QTL and Links Developmental Environment to Central Corneal Thickness Determination

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Egr-1 is a key regulator of the blood-brain barrier damage induced by meningitic Escherichia coli

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