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

Abstract

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.

Cardiac contraction and relaxation are regulated by beta 1 adrenergic receptor-generated cAMP pools at distinct membrane locations

“…The processes for neonatal cardiomyocytes isolation are modified from previous research 84 . Briefly, hearts harvested from P1-2 neonatal CD1 pups were tear into small pieces in the ice-cold HBSS containing 20 mM HEPES.…”

Role and Mechanism of PKC-δ for Cardiovascular Disease: Current Status and Perspective

“…In addition, PKC-δ has genetic polymorphisms, and conditional knockout mice can be generated through splicing of the PKC- δ gene, Prkcd. Conditional knockout mice are generated by regulating expression of exons ( 42 ). Conditional general PKC-δ knockout mice were generated by knockout of PKC-δ encoding gene (by deleting shared exons of PKC-δ I, II, IV, V, VI, and VII) through Cre-Lox recombination ( 42 ).…”

“…Conditional knockout mice are generated by regulating expression of exons ( 42 ). Conditional general PKC-δ knockout mice were generated by knockout of PKC-δ encoding gene (by deleting shared exons of PKC-δ I, II, IV, V, VI, and VII) through Cre-Lox recombination ( 42 ). In addition, conditional specific PKC-δ-suptype knockout mice were also reported.…”

“…In current studies, PKC-δ −/− mice are mostly the knockout of PKC-δ I and II subtypes. Recently, Niino et al generated a conditional knockout mice lack of PKC-δ I or II, IV, V, VI, and VII ( 42 ). Their study found that a wide range of PKC-δ subtypes knockout can inhibit fetal development and is associated with adult mice heart elastic fiber hyperplasia and lung inflammation ( 42 ).…”

Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria

“…Prkcd fl/fl mice on the B6 background were developed by Drs. Niino, Shioda and Sakimura (Niino et al, 2021) and purchased from the RIKEN BioResource Center (RBRC06462). Mice were immunized i.p.…”