Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice.
<p>Mutations in the X-linked gene <em>Protocadherin-19</em> (<em>Pcdh19</em>) cause female-limited epilepsy and mental retardation in humans. Although <em>Pcdh19</em> is known to be a homophilic cell-cell adhesion molecule, how its mutations bring about fema...
| Những tác giả chính: | , , , , , , |
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| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
Nature
2017
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| _version_ | 1826282866890244096 |
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| author | Hayashi, S Inoue, Y Hattori, S Kaneko, M Shioi, G Miyakawa, T Takeichi, M |
| author_facet | Hayashi, S Inoue, Y Hattori, S Kaneko, M Shioi, G Miyakawa, T Takeichi, M |
| author_sort | Hayashi, S |
| collection | OXFORD |
| description | <p>Mutations in the X-linked gene <em>Protocadherin-19</em> (<em>Pcdh19</em>) cause female-limited epilepsy and mental retardation in humans. Although <em>Pcdh19</em> is known to be a homophilic cell-cell adhesion molecule, how its mutations bring about female-specific disorders remains elusive. Here, we report the effects of <em>Pcdh19</em> knockout in mice on their development and behavior. <em>Pcdh19</em> was expressed in various brain regions including the cerebral cortex and hippocampus. Although <em>Pcdh19</em>-positive cells were evenly distributed in layer V of wild-type cortices, their distribution became a mosaic in <em>Pcdh19</em> heterozygous female cortices. In cortical and hippocampal neurons, <em>Pcdh19</em> was localized along their dendrites, showing occasional accumulation on synapses. <em>Pcdh19</em> mutants, however, displayed no detectable abnormalities in dendrite and spine morphology of layer V neurons. Nevertheless, <em>Pcdh19</em> hemizygous males and heterozygous females showed impaired behaviors including activity defects under stress conditions. Notably, only heterozygous females exhibited decreased fear responses. In addition, <em>Pcdh19</em> overexpression in wild-type cortices led to ectopic clustering of <em>Pcdh19</em>-positive neurons. These results suggest that <em>Pcdh19</em> is required for behavioral control in mice, but its genetic loss differentially affects the male and female behavior, as seen in human, and they also support the hypothesis that the mosaic expression of <em>Pcdh19</em> in brains perturbs neuronal interactions.</p> |
| first_indexed | 2024-03-07T00:50:19Z |
| format | Journal article |
| id | oxford-uuid:862a8a40-9ef7-45ae-b08e-93b211cdad56 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:50:19Z |
| publishDate | 2017 |
| publisher | Nature |
| record_format | dspace |
| spelling | oxford-uuid:862a8a40-9ef7-45ae-b08e-93b211cdad562022-03-26T22:02:14ZLoss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:862a8a40-9ef7-45ae-b08e-93b211cdad56EnglishSymplectic Elements at OxfordNature2017Hayashi, SInoue, YHattori, SKaneko, MShioi, GMiyakawa, TTakeichi, M<p>Mutations in the X-linked gene <em>Protocadherin-19</em> (<em>Pcdh19</em>) cause female-limited epilepsy and mental retardation in humans. Although <em>Pcdh19</em> is known to be a homophilic cell-cell adhesion molecule, how its mutations bring about female-specific disorders remains elusive. Here, we report the effects of <em>Pcdh19</em> knockout in mice on their development and behavior. <em>Pcdh19</em> was expressed in various brain regions including the cerebral cortex and hippocampus. Although <em>Pcdh19</em>-positive cells were evenly distributed in layer V of wild-type cortices, their distribution became a mosaic in <em>Pcdh19</em> heterozygous female cortices. In cortical and hippocampal neurons, <em>Pcdh19</em> was localized along their dendrites, showing occasional accumulation on synapses. <em>Pcdh19</em> mutants, however, displayed no detectable abnormalities in dendrite and spine morphology of layer V neurons. Nevertheless, <em>Pcdh19</em> hemizygous males and heterozygous females showed impaired behaviors including activity defects under stress conditions. Notably, only heterozygous females exhibited decreased fear responses. In addition, <em>Pcdh19</em> overexpression in wild-type cortices led to ectopic clustering of <em>Pcdh19</em>-positive neurons. These results suggest that <em>Pcdh19</em> is required for behavioral control in mice, but its genetic loss differentially affects the male and female behavior, as seen in human, and they also support the hypothesis that the mosaic expression of <em>Pcdh19</em> in brains perturbs neuronal interactions.</p> |
| spellingShingle | Hayashi, S Inoue, Y Hattori, S Kaneko, M Shioi, G Miyakawa, T Takeichi, M Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice. |
| title | Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice. |
| title_full | Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice. |
| title_fullStr | Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice. |
| title_full_unstemmed | Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice. |
| title_short | Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice. |
| title_sort | loss of x linked protocadherin 19 differentially affects the behavior of heterozygous female and hemizygous male mice |
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