Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice

Purpose: The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a...

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Autores principales:	Wei-Hao Peng, Meng-Lin Liao, Wan-Chun Huang, Pei-Kang Liu, Sarah R. Levi, Yun-Ju Tseng, Chia-Ying Lee, Lung-Kun Yeh, Kuan-Jen Chen, Chung-Liang Chien, Nan-Kai Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	GDNF family of ligands (GFL) rearranged during transfection (RET) mouse retina ribbon synapses Cre-loxP knockout mice Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/ea6c5e3eba6e4b49aa81208f1eb3b603
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spelling	oai:doaj.org-article:ea6c5e3eba6e4b49aa81208f1eb3b6032021-11-05T10:27:08ZConditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice1662-453X10.3389/fnins.2021.728905https://doaj.org/article/ea6c5e3eba6e4b49aa81208f1eb3b6032021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.728905/fullhttps://doaj.org/toc/1662-453XPurpose: The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a result of renal underdevelopment. To extend the observation period, we generated the Ret conditional knockout Chx10-Cre;C-Retlx/lx mouse model and analyzed the retinal function and morphological changes in mature and aging Chx10-Cre;C-Retlx/lx mice.Methods: Retina-specific depletion of Ret was achieved using mice with floxed alleles of the Ret gene with CHX10-driven Cre recombinase; floxed mice without Cre expression were used as controls. Retinal function was examined using electroretinography (ERG), and 2-, 4-, 12-, and 24-month-old mice were analyzed by hematoxylin staining and immunohistochemistry to evaluate retinal morphological alterations. The ultrastructure of photoreceptor synapses was evaluated using electron microscopy.Results: The results of the ERG testing showed that b-wave amplitudes were reduced in Chx10-Cre;C-Retlx/lx mice, whereas a-waves were not affected. A histopathological analysis revealed a thinner and disorganized outer plexiform layer at the ages of 12 and 24 months in Chx10-Cre;C-Retlx/lx mice. Moreover, the data provided by immunohistochemistry showed defects in the synapses of photoreceptor cells. This result was confirmed at the ultrastructural level, thus supporting the participation of Ret in the morphological changes of the synaptic ribbon.Conclusion: Our results provide evidence of the role of Ret in maintaining the function of the retina, which was essential for preserving the structure of the synaptic ribbon and supporting the integrity of the outer plexiform layer.Wei-Hao PengMeng-Lin LiaoWan-Chun HuangPei-Kang LiuPei-Kang LiuPei-Kang LiuPei-Kang LiuSarah R. LeviYun-Ju TsengChia-Ying LeeLung-Kun YehLung-Kun YehKuan-Jen ChenKuan-Jen ChenChung-Liang ChienNan-Kai WangFrontiers Media S.A.articleGDNF family of ligands (GFL)rearranged during transfection (RET)mouse retinaribbon synapsesCre-loxP knockout miceNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GDNF family of ligands (GFL) rearranged during transfection (RET) mouse retina ribbon synapses Cre-loxP knockout mice Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	GDNF family of ligands (GFL) rearranged during transfection (RET) mouse retina ribbon synapses Cre-loxP knockout mice Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Wei-Hao Peng Meng-Lin Liao Wan-Chun Huang Pei-Kang Liu Pei-Kang Liu Pei-Kang Liu Pei-Kang Liu Sarah R. Levi Yun-Ju Tseng Chia-Ying Lee Lung-Kun Yeh Lung-Kun Yeh Kuan-Jen Chen Kuan-Jen Chen Chung-Liang Chien Nan-Kai Wang Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
description	Purpose: The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a result of renal underdevelopment. To extend the observation period, we generated the Ret conditional knockout Chx10-Cre;C-Retlx/lx mouse model and analyzed the retinal function and morphological changes in mature and aging Chx10-Cre;C-Retlx/lx mice.Methods: Retina-specific depletion of Ret was achieved using mice with floxed alleles of the Ret gene with CHX10-driven Cre recombinase; floxed mice without Cre expression were used as controls. Retinal function was examined using electroretinography (ERG), and 2-, 4-, 12-, and 24-month-old mice were analyzed by hematoxylin staining and immunohistochemistry to evaluate retinal morphological alterations. The ultrastructure of photoreceptor synapses was evaluated using electron microscopy.Results: The results of the ERG testing showed that b-wave amplitudes were reduced in Chx10-Cre;C-Retlx/lx mice, whereas a-waves were not affected. A histopathological analysis revealed a thinner and disorganized outer plexiform layer at the ages of 12 and 24 months in Chx10-Cre;C-Retlx/lx mice. Moreover, the data provided by immunohistochemistry showed defects in the synapses of photoreceptor cells. This result was confirmed at the ultrastructural level, thus supporting the participation of Ret in the morphological changes of the synaptic ribbon.Conclusion: Our results provide evidence of the role of Ret in maintaining the function of the retina, which was essential for preserving the structure of the synaptic ribbon and supporting the integrity of the outer plexiform layer.
format	article
author	Wei-Hao Peng Meng-Lin Liao Wan-Chun Huang Pei-Kang Liu Pei-Kang Liu Pei-Kang Liu Pei-Kang Liu Sarah R. Levi Yun-Ju Tseng Chia-Ying Lee Lung-Kun Yeh Lung-Kun Yeh Kuan-Jen Chen Kuan-Jen Chen Chung-Liang Chien Nan-Kai Wang
author_facet	Wei-Hao Peng Meng-Lin Liao Wan-Chun Huang Pei-Kang Liu Pei-Kang Liu Pei-Kang Liu Pei-Kang Liu Sarah R. Levi Yun-Ju Tseng Chia-Ying Lee Lung-Kun Yeh Lung-Kun Yeh Kuan-Jen Chen Kuan-Jen Chen Chung-Liang Chien Nan-Kai Wang
author_sort	Wei-Hao Peng
title	Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
title_short	Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
title_full	Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
title_fullStr	Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
title_full_unstemmed	Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
title_sort	conditional deletion of activating rearranged during transfection receptor tyrosine kinase leads to impairment of photoreceptor ribbon synapses and disrupted visual function in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ea6c5e3eba6e4b49aa81208f1eb3b603
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Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice

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