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 Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Elastic Tissue/*pathology ; Fetal Development/*genetics ; Lung/*pathology ; Pneumonia/*genetics ; Protein Kinase C-delta/*deficiency; Animals ; Disease Models, Animal ; Elastic Tissue/immunology ; Female ; Humans ; Hyperplasia/genetics ; Hyperplasia/pathology ; Lung/immunology ; Male ; Mice ; Mice, Knockout ; Pneumonia/immunology ; Pneumonia/pathology ; Protein Kinase C-delta/genetics

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.
Competing Interests: The authors have declared that no competing interests exist.

Semin Cancer Biol. 2018 Feb;48:18-26. (PMID: 28476658)
Blood. 2013 Apr 18;121(16):3117-25. (PMID: 23430113)
J Clin Invest. 2001 Nov;108(10):1505-12. (PMID: 11714742)
Am J Physiol Heart Circ Physiol. 2001 Nov;281(5):H2062-71. (PMID: 11668067)
Cell Signal. 2007 May;19(5):892-901. (PMID: 17336499)
EMBO J. 1995 Dec 15;14(24):6148-56. (PMID: 8557034)
Biochemistry. 2008 Jan 15;47(2):787-97. (PMID: 18092819)
Neurosci Res. 2007 Jun;58(2):105-12. (PMID: 17298852)
Oncogene. 1999 Feb 4;18(5):1251-6. (PMID: 10022132)
Sci Signal. 2015 Apr 21;8(373):ra39. (PMID: 25900833)
Aging Cell. 2009 Jun;8(3):277-87. (PMID: 19627267)
Biochem Biophys Res Commun. 2000 Mar 16;269(2):557-63. (PMID: 10708593)
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10159-63. (PMID: 1438205)
Int J Mol Sci. 2019 Mar 26;20(6):. (PMID: 30917487)
Circ Res. 2017 Oct 27;121(10):1153-1167. (PMID: 28855204)
Mol Reprod Dev. 2015 Oct;82(10):797-808. (PMID: 26202826)
Genomics. 2003 Jul;82(1):57-67. (PMID: 12809676)
J Clin Immunol. 2016 Oct;36(7):631-40. (PMID: 27541826)
Cancer Lett. 2016 Jul 28;377(2):158-63. (PMID: 27130668)
Dev Cell. 2007 Jan;12(1):113-27. (PMID: 17199045)
J Exp Med. 1996 Dec 1;184(6):2399-404. (PMID: 8976194)
PLoS One. 2013 Aug 08;8(8):e70815. (PMID: 23951014)
Arthritis Rheum. 2013 Aug;65(8):2161-71. (PMID: 23666743)
FEBS Lett. 2006 May 1;580(10):2458-64. (PMID: 16638571)
J Biol Chem. 2012 Mar 16;287(12):9299-310. (PMID: 22275369)
Biochem Biophys Res Commun. 2011 Jul 1;410(2):177-82. (PMID: 21549093)
Gene Expr. 2006;13(2):73-84. (PMID: 17017122)
Gastroenterology. 2011 Nov;141(5):1720-7. (PMID: 21704002)
Clin Transl Oncol. 2015 May;17(5):371-7. (PMID: 25351171)
EMBO J. 2002 Nov 15;21(22):6050-60. (PMID: 12426377)
Cell Death Dis. 2019 Feb 15;10(3):156. (PMID: 30770789)
J Cancer Res Clin Oncol. 2007 Nov;133(11):793-808. (PMID: 17661083)
J Cell Physiol. 2012 May;227(5):1899-910. (PMID: 21732361)
Oncogene. 2005 Apr 21;24(18):3067-72. (PMID: 15735725)
Int J Mol Sci. 2020 Apr 09;21(7):. (PMID: 32283691)
ScientificWorldJournal. 2010 Nov 16;10:2272-84. (PMID: 21103796)
Biol Pharm Bull. 2001 Sep;24(9):973-7. (PMID: 11558579)
J Biol Chem. 2010 Aug 20;285(34):25987-95. (PMID: 20547768)
Nature. 2002 Apr 25;416(6883):865-9. (PMID: 11976687)
Aging Dis. 2018 Aug 1;9(4):647-663. (PMID: 30090653)
J Biol Chem. 1998 Nov 6;273(45):29995-30002. (PMID: 9792720)
Mol Cell Biol. 1999 Dec;19(12):8547-58. (PMID: 10567579)
Nature. 2002 Apr 25;416(6883):860-5. (PMID: 11976686)
J Biol Chem. 2006 Apr 7;281(14):9728-37. (PMID: 16452485)
Cell Death Differ. 2000 Dec;7(12):1200-9. (PMID: 11175257)
Dev Growth Differ. 2005 Jan;47(1):15-24. (PMID: 15740583)
J Biochem. 2002 Dec;132(6):831-9. (PMID: 12473183)
J Biol Chem. 1977 Nov 10;252(21):7603-9. (PMID: 199593)
Science. 1992 Oct 23;258(5082):607-14. (PMID: 1411571)
J Neuroinflammation. 2018 Nov 6;15(1):309. (PMID: 30400800)
Physiol Rev. 2008 Oct;88(4):1341-78. (PMID: 18923184)

EC 2.7.1.- (Prkcd protein, mouse)
EC 2.7.11.13 (Protein Kinase C-delta)

Date Created: 20210701 Date Completed: 20211117 Latest Revision: 20211117

20240829

PMC8248728

10.1371/journal.pone.0253912

34197550