Genetic Background-Dependent Role of Egr1 for Eyelid Development

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-/- C57BL/6-background mice have normal eyelid development, but back-crossing to BALB/c background for 4-5 generations resulted in defective eyelid development by embryonic day E15.5, at which time EGR1 was expressed in eyelids of WT mice. Defective eyelid formation correlated with profound ocular anomalies evident by post-natal 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, as 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. RNA-Seq analyses using total RNA from eyes of newborn and adult Egr1-/- BALB/c mice, and total RNA from each eye of three 3-day old Egr1-/- mice with unmerged eyelids as well as Egr1+/- littermate controls