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:	Yuko S Niino, Ikuo Kawashima, Yoshinobu Iguchi, Hiroaki Kanda, Kiyoshi Ogura, Kaoru Mita-Yoshida, Tomio Ono, Maya Yamazaki, Kenji Sakimura, Satomi Yogosawa, Kiyotsugu Yoshida, Seiji Shioda, Takaya Gotoh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9aeae0a7358643b3bccee12c21878958
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spelling	oai:doaj.org-article:9aeae0a7358643b3bccee12c218789582021-12-02T20:09:43ZPKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice.1932-620310.1371/journal.pone.0253912https://doaj.org/article/9aeae0a7358643b3bccee12c218789582021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253912https://doaj.org/toc/1932-6203Protein 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.Yuko S NiinoIkuo KawashimaYoshinobu IguchiHiroaki KandaKiyoshi OguraKaoru Mita-YoshidaTomio OnoMaya YamazakiKenji SakimuraSatomi YogosawaKiyotsugu YoshidaSeiji ShiodaTakaya GotohPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253912 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuko S Niino Ikuo Kawashima Yoshinobu Iguchi Hiroaki Kanda Kiyoshi Ogura Kaoru Mita-Yoshida Tomio Ono Maya Yamazaki Kenji Sakimura Satomi Yogosawa Kiyotsugu Yoshida Seiji Shioda Takaya Gotoh PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice.
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.
format	article
author	Yuko S Niino Ikuo Kawashima Yoshinobu Iguchi Hiroaki Kanda Kiyoshi Ogura Kaoru Mita-Yoshida Tomio Ono Maya Yamazaki Kenji Sakimura Satomi Yogosawa Kiyotsugu Yoshida Seiji Shioda Takaya Gotoh
author_facet	Yuko S Niino Ikuo Kawashima Yoshinobu Iguchi Hiroaki Kanda Kiyoshi Ogura Kaoru Mita-Yoshida Tomio Ono Maya Yamazaki Kenji Sakimura Satomi Yogosawa Kiyotsugu Yoshida Seiji Shioda Takaya Gotoh
author_sort	Yuko S Niino
title	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_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_sort	pkcδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult pkcδ knockout mice.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9aeae0a7358643b3bccee12c21878958
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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.

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