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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 |
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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 |
format | article |
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−/− 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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1705848114</identifier><identifier>PMID: 28778995</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2017-08, Vol.114 (34), p.E7131-E7139</ispartof><rights>Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Aug 22, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-21959fc8e3eb4e6fb6e2c19a7edb1f4de7ac3eab6e3ec316bdb6abf0c4d71a7a3</citedby><cites>FETCH-LOGICAL-c443t-21959fc8e3eb4e6fb6e2c19a7edb1f4de7ac3eab6e3ec316bdb6abf0c4d71a7a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26487331$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26487331$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791,58236,58469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28778995$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oh, Jangsuk</creatorcontrib><creatorcontrib>Wang, Yujuan</creatorcontrib><creatorcontrib>Chen, Shida</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Du, Ning</creatorcontrib><creatorcontrib>Yu, Zu-Xi</creatorcontrib><creatorcontrib>Butcher, Donna</creatorcontrib><creatorcontrib>Gebregiorgis, Tesfay</creatorcontrib><creatorcontrib>Strachan, Erin</creatorcontrib><creatorcontrib>Lehmann, Ordan J.</creatorcontrib><creatorcontrib>Brooks, Brian P.</creatorcontrib><creatorcontrib>Chan, Chi-Chao</creatorcontrib><creatorcontrib>Leonard, Warren J.</creatorcontrib><title>Genetic background-dependent role of Egr1 for eyelid development</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><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.</description><subject>Abnormalities</subject><subject>Animals</subject><subject>Anophthalmia</subject><subject>Biological Sciences</subject><subject>Calcification</subject><subject>Cataracts</subject><subject>Cornea</subject><subject>Differentiation</subject><subject>Dysplasia</subject><subject>Early Growth Response Protein 1 - genetics</subject><subject>Early Growth Response Protein 1 - metabolism</subject><subject>EGR-1 protein</subject><subject>Enzymes</subject><subject>Eye</subject><subject>Eye - growth & development</subject><subject>Eye - metabolism</subject><subject>Eyelid</subject><subject>Eyelids - growth & development</subject><subject>Eyelids - metabolism</subject><subject>Eyes & eyesight</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genotype & phenotype</subject><subject>Keratitis</subject><subject>Mice</subject><subject>Mice - genetics</subject><subject>Mice - growth & development</subject><subject>Mice - metabolism</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microphthalmia</subject><subject>Neuroplasticity</subject><subject>PNAS Plus</subject><subject>Retina</subject><subject>Studies</subject><subject>Tumor suppression</subject><subject>Tyrosinase</subject><subject>Vascularization</subject><subject>Zinc finger proteins</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpdkU1P3DAQhq2KqmwXzj1RReLSS8ATO_64IBCiWySkXuBsOfZkmyUbp3aCxL-vV0uh5TTSzDPvfLyEfAF6BlSy83Gw6QwkrRVXAPwDWQDVUAqu6QFZUFrJUvGKH5LPKW0opbpW9BM5rJSUSut6QS5XOODUuaKx7nEdwzz40uOIg8dhKmLosQhtcbOOULQhFviMfecLj0_Yh3GbmSPysbV9wuOXuCQP32_ur3-Udz9Xt9dXd6XjnE1lBbrWrVPIsOEo2kZg5UBbib6BlnuU1jG0Oc3QMRCNb4RtWuq4l2ClZUtysdcd52aL3uXR0fZmjN3WxmcTbGf-rwzdL7MOT6aupVBAs8C3F4EYfs-YJrPtksO-twOGORnQlRBK1lxn9PQduglzHPJ5meKCs_zqneD5nnIxpBSxfV0GqNm5Y3bumDd3csfXf2945f_akYGTPbBJU4hvdcGVZAzYHzcClwI</recordid><startdate>20170822</startdate><enddate>20170822</enddate><creator>Oh, Jangsuk</creator><creator>Wang, Yujuan</creator><creator>Chen, Shida</creator><creator>Li, Peng</creator><creator>Du, Ning</creator><creator>Yu, Zu-Xi</creator><creator>Butcher, Donna</creator><creator>Gebregiorgis, Tesfay</creator><creator>Strachan, Erin</creator><creator>Lehmann, Ordan J.</creator><creator>Brooks, Brian P.</creator><creator>Chan, Chi-Chao</creator><creator>Leonard, Warren J.</creator><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170822</creationdate><title>Genetic background-dependent role of Egr1 for eyelid development</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-21959fc8e3eb4e6fb6e2c19a7edb1f4de7ac3eab6e3ec316bdb6abf0c4d71a7a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Abnormalities</topic><topic>Animals</topic><topic>Anophthalmia</topic><topic>Biological Sciences</topic><topic>Calcification</topic><topic>Cataracts</topic><topic>Cornea</topic><topic>Differentiation</topic><topic>Dysplasia</topic><topic>Early Growth Response Protein 1 - genetics</topic><topic>Early Growth Response Protein 1 - metabolism</topic><topic>EGR-1 protein</topic><topic>Enzymes</topic><topic>Eye</topic><topic>Eye - growth & development</topic><topic>Eye - metabolism</topic><topic>Eyelid</topic><topic>Eyelids - growth & development</topic><topic>Eyelids - metabolism</topic><topic>Eyes & eyesight</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genotype & phenotype</topic><topic>Keratitis</topic><topic>Mice</topic><topic>Mice - genetics</topic><topic>Mice - growth & development</topic><topic>Mice - metabolism</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microphthalmia</topic><topic>Neuroplasticity</topic><topic>PNAS Plus</topic><topic>Retina</topic><topic>Studies</topic><topic>Tumor suppression</topic><topic>Tyrosinase</topic><topic>Vascularization</topic><topic>Zinc finger proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oh, Jangsuk</creatorcontrib><creatorcontrib>Wang, Yujuan</creatorcontrib><creatorcontrib>Chen, Shida</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Du, Ning</creatorcontrib><creatorcontrib>Yu, Zu-Xi</creatorcontrib><creatorcontrib>Butcher, Donna</creatorcontrib><creatorcontrib>Gebregiorgis, Tesfay</creatorcontrib><creatorcontrib>Strachan, Erin</creatorcontrib><creatorcontrib>Lehmann, Ordan J.</creatorcontrib><creatorcontrib>Brooks, Brian P.</creatorcontrib><creatorcontrib>Chan, Chi-Chao</creatorcontrib><creatorcontrib>Leonard, Warren J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oh, Jangsuk</au><au>Wang, Yujuan</au><au>Chen, Shida</au><au>Li, Peng</au><au>Du, Ning</au><au>Yu, Zu-Xi</au><au>Butcher, Donna</au><au>Gebregiorgis, Tesfay</au><au>Strachan, Erin</au><au>Lehmann, Ordan J.</au><au>Brooks, Brian P.</au><au>Chan, Chi-Chao</au><au>Leonard, Warren J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic background-dependent role of Egr1 for eyelid development</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2017-08-22</date><risdate>2017</risdate><volume>114</volume><issue>34</issue><spage>E7131</spage><epage>E7139</epage><pages>E7131-E7139</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>28778995</pmid><doi>10.1073/pnas.1705848114</doi><oa>free_for_read</oa></addata></record> |
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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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