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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 −/− mice on the C57BL/6 background have normal eyelid development, but back-crossing to BALB/c ba...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2017-08, Vol.114 (34), p.E7131-E7139
Main Authors: Oh, Jangsuk, Wang, Yujuan, Chen, Shida, Li, Peng, Du, Ning, Yu, Zu-Xi, Butcher, Donna, Gebregiorgis, Tesfay, Strachan, Erin, Lehmann, Ordan J., Brooks, Brian P., Chan, Chi-Chao, Leonard, Warren J.
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cites cdi_FETCH-LOGICAL-c443t-21959fc8e3eb4e6fb6e2c19a7edb1f4de7ac3eab6e3ec316bdb6abf0c4d71a7a3
container_end_page E7139
container_issue 34
container_start_page E7131
container_title Proceedings of the National Academy of Sciences - PNAS
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creator Oh, Jangsuk
Wang, Yujuan
Chen, Shida
Li, Peng
Du, Ning
Yu, Zu-Xi
Butcher, Donna
Gebregiorgis, Tesfay
Strachan, Erin
Lehmann, Ordan J.
Brooks, Brian P.
Chan, Chi-Chao
Leonard, Warren J.
description 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.
doi_str_mv 10.1073/pnas.1705848114
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source JSTOR Archival Journals; PubMed Central
subjects Abnormalities
Animals
Anophthalmia
Biological Sciences
Calcification
Cataracts
Cornea
Differentiation
Dysplasia
Early Growth Response Protein 1 - genetics
Early Growth Response Protein 1 - metabolism
EGR-1 protein
Enzymes
Eye
Eye - growth & development
Eye - metabolism
Eyelid
Eyelids - growth & development
Eyelids - metabolism
Eyes & eyesight
Gene Expression Regulation, Developmental
Genotype & phenotype
Keratitis
Mice
Mice - genetics
Mice - growth & development
Mice - metabolism
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Microphthalmia
Neuroplasticity
PNAS Plus
Retina
Studies
Tumor suppression
Tyrosinase
Vascularization
Zinc finger proteins
title Genetic background-dependent role of Egr1 for eyelid development
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