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The specific requirements of MKK4 and MKK7 in retinal development and retinal ganglion cell (RGC) death after axonal injury, however, are currently undefined. Optic nerve injury is an important insult in many neurologic conditions including traumatic, ischemic, inflammatory, and glaucomatous optic neuropathies. Mice deficient in\n                    <jats:italic>Mkk4<\/jats:italic>\n                    ,\n                    <jats:italic>Mkk7<\/jats:italic>\n                    , and both\n                    <jats:italic>Mkk4<\/jats:italic>\n                    and\n                    <jats:italic>Mkk7<\/jats:italic>\n                    were generated. Immunohistochemistry was used to study the distribution and structure of retinal cell types and to assess RGC survival after optic nerve injury (mechanical controlled optic nerve crush (CONC)). Adult\n                    <jats:italic>Mkk4<\/jats:italic>\n                    - and\n                    <jats:italic>Mkk7-<\/jats:italic>\n                    deficient retinas had all retinal cell types, and with the exception of small areas of disrupted photoreceptor lamination in\n                    <jats:italic>Mkk4<\/jats:italic>\n                    -deficient mice, the retinas of both mutants were grossly normal. Deficiency of\n                    <jats:italic>Mkk4<\/jats:italic>\n                    or\n                    <jats:italic>Mkk7<\/jats:italic>\n                    reduced JNK signaling in RGCs after axonal injury and resulted in a significantly greater percentage of surviving RGCs 35 days after CONC as compared to wild-type controls (\n                    <jats:italic>Mkk4<\/jats:italic>\n                    : 51.5%,\n                    <jats:italic>Mkk7:<\/jats:italic>\n                    29.1%, WT: 15.2%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Combined deficiency of\n                    <jats:italic>Mkk4<\/jats:italic>\n                    and\n                    <jats:italic>Mkk7<\/jats:italic>\n                    caused failure of optic nerve formation, irregular retinal axonal trajectories, disruption of retinal lamination, clumping of RGC bodies, and dendritic fasciculation of dopaminergic amacrine cells. These results suggest that MKK4 and MKK7 may serve redundant and unique roles in molecular signaling important for retinal development and injury response following axonal insult.\n                  <\/jats:p>","DOI":"10.1038\/s41419-018-1079-7","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T04:07:42Z","timestamp":1540526862000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death"],"prefix":"10.1038","volume":"9","author":[{"given":"Stephanie B.","family":"Syc-Mazurek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-7632","authenticated-orcid":false,"given":"Richard T.","family":"Libby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"1079_CR1","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","volume":"1802","author":"EK Kim","year":"2010","unstructured":"Kim, E. 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