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PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice

Protein kinase C-delta (PKCδ) has a caspase-3 recognition sequence in its structure, suggesting its involvement in apoptosis. In addition, PKCδ was recently reported to function as an anti-cancer factor. The generation of a PKCδ knockout mouse model indicated that PKCδ plays a role in B cell homeost...

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Autores principales: Niino, Yuko S., Kawashima, Ikuo, Iguchi, Yoshinobu, Kanda, Hiroaki, Ogura, Kiyoshi, Mita-Yoshida, Kaoru, Ono, Tomio, Yamazaki, Maya, Sakimura, Kenji, Yogosawa, Satomi, Yoshida, Kiyotsugu, Shioda, Seiji, Gotoh, Takaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248728/
https://www.ncbi.nlm.nih.gov/pubmed/34197550
http://dx.doi.org/10.1371/journal.pone.0253912
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author Niino, Yuko S.
Kawashima, Ikuo
Iguchi, Yoshinobu
Kanda, Hiroaki
Ogura, Kiyoshi
Mita-Yoshida, Kaoru
Ono, Tomio
Yamazaki, Maya
Sakimura, Kenji
Yogosawa, Satomi
Yoshida, Kiyotsugu
Shioda, Seiji
Gotoh, Takaya
author_facet Niino, Yuko S.
Kawashima, Ikuo
Iguchi, Yoshinobu
Kanda, Hiroaki
Ogura, Kiyoshi
Mita-Yoshida, Kaoru
Ono, Tomio
Yamazaki, Maya
Sakimura, Kenji
Yogosawa, Satomi
Yoshida, Kiyotsugu
Shioda, Seiji
Gotoh, Takaya
author_sort Niino, Yuko S.
collection PubMed
description Protein kinase C-delta (PKCδ) has a caspase-3 recognition sequence in its structure, suggesting its involvement in apoptosis. In addition, PKCδ was recently reported to function as an anti-cancer factor. The generation of a PKCδ knockout mouse model indicated that PKCδ plays a role in B cell homeostasis. However, the Pkcrd gene, which is regulated through complex transcription, produces multiple proteins via alternative splicing. Since gene mutations can result in the loss of function of molecular species required for each tissue, in the present study, conditional PKCδ knockout mice lacking PKCδI, II, IV, V, VI, and VII were generated to enable tissue-specific deletion of PKCδ using a suitable Cre mouse. We generated PKCδ-null mice that lacked whole-body expression of PKCδ. PKCδ+/- parental mice gave birth to only 3.4% PKCδ-/- offsprings that deviated significantly from the expected Mendelian ratio (χ2(2) = 101.7, P < 0.001). Examination of mice on embryonic day 11.5 (E11.5) showed the proportion of PKCδ-/- mice implanted in the uterus in accordance with Mendelian rules; however, approximately 70% of the fetuses did not survive at E11.5. PKCδ-/- mice that survived until adulthood showed enlarged spleens, with some having cardiac and pulmonary abnormalities. Our findings suggest that the lack of PKCδ may have harmful effects on fetal development, and heart and lung functions after birth. Furthermore, our study provides a reference for future studies on PKCδ deficient mice that would elucidate the effects of the multiple protein variants in mice and decipher the roles of PKCδ in various diseases.
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spelling pubmed-82487282021-07-09 PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice Niino, Yuko S. Kawashima, Ikuo Iguchi, Yoshinobu Kanda, Hiroaki Ogura, Kiyoshi Mita-Yoshida, Kaoru Ono, Tomio Yamazaki, Maya Sakimura, Kenji Yogosawa, Satomi Yoshida, Kiyotsugu Shioda, Seiji Gotoh, Takaya PLoS One Research Article Protein kinase C-delta (PKCδ) has a caspase-3 recognition sequence in its structure, suggesting its involvement in apoptosis. In addition, PKCδ was recently reported to function as an anti-cancer factor. The generation of a PKCδ knockout mouse model indicated that PKCδ plays a role in B cell homeostasis. However, the Pkcrd gene, which is regulated through complex transcription, produces multiple proteins via alternative splicing. Since gene mutations can result in the loss of function of molecular species required for each tissue, in the present study, conditional PKCδ knockout mice lacking PKCδI, II, IV, V, VI, and VII were generated to enable tissue-specific deletion of PKCδ using a suitable Cre mouse. We generated PKCδ-null mice that lacked whole-body expression of PKCδ. PKCδ+/- parental mice gave birth to only 3.4% PKCδ-/- offsprings that deviated significantly from the expected Mendelian ratio (χ2(2) = 101.7, P < 0.001). Examination of mice on embryonic day 11.5 (E11.5) showed the proportion of PKCδ-/- mice implanted in the uterus in accordance with Mendelian rules; however, approximately 70% of the fetuses did not survive at E11.5. PKCδ-/- mice that survived until adulthood showed enlarged spleens, with some having cardiac and pulmonary abnormalities. Our findings suggest that the lack of PKCδ may have harmful effects on fetal development, and heart and lung functions after birth. Furthermore, our study provides a reference for future studies on PKCδ deficient mice that would elucidate the effects of the multiple protein variants in mice and decipher the roles of PKCδ in various diseases. Public Library of Science 2021-07-01 /pmc/articles/PMC8248728/ /pubmed/34197550 http://dx.doi.org/10.1371/journal.pone.0253912 Text en © 2021 Niino et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Niino, Yuko S.
Kawashima, Ikuo
Iguchi, Yoshinobu
Kanda, Hiroaki
Ogura, Kiyoshi
Mita-Yoshida, Kaoru
Ono, Tomio
Yamazaki, Maya
Sakimura, Kenji
Yogosawa, Satomi
Yoshida, Kiyotsugu
Shioda, Seiji
Gotoh, Takaya
PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice
title PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice
title_full PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice
title_fullStr PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice
title_full_unstemmed PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice
title_short PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice
title_sort pkcδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult pkcδ knockout mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248728/
https://www.ncbi.nlm.nih.gov/pubmed/34197550
http://dx.doi.org/10.1371/journal.pone.0253912
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