Protein kinase D is essential for embryonic survival through functionally redundant subtypes.

AIMS: Protein kinase D (PKD) is a family of serine/threonine kinases encoded by three genes-Prkd1, Prkd2, and Prkd3. PKD has been implicated in regulating cell proliferation, apoptosis, motility, and protein trafficking, but its physiological roles during embryonic development remain incompletely understood. In this study, we aimed to investigate the effects of PKD deletion on embryonic survival and development in mice.

MATERIALS AND

METHODS

Single knockout mice for each PKD isoform (Prkd1-/-, Prkd2-/-, and Prkd3-/-, referred to as D1KO, D2KO, and D3KO, respectively) were generated and bred with each other to produce compound double knockout (DKO) models. Genotypic and histological analysis were performed to determine embryonic viability and morphology.

KEY FINDINGS: Single knockout mice of any PKD isoform exhibited normal embryonic development and postnatal survival with Mendelian inheritance patterns. However, deletion of both Prkd1 and Prkd2 (DKO1/2) or both Prkd1 and Prkd3 (DKO1/3) caused severe allantoic-placental defects, including reduced umbilical vessel size and decreased placental labyrinth depth. These defects led to growth retardation, pericardial edema, and embryonic lethality between embryonic day 10.5 (E10.5) and E11.5 with full penetrance. In contrast, deletion of Prkd2 and Prkd3 (DKO2/3) also caused embryonic lethality, but with partial penetrance and at a later stage. Although over 50 % of DKO2/3 embryos survived to E18.5, they exhibited marked growth retardation, as evidenced by reduced body weight and smaller organ size.

SIGNIFICANCE: Our results demonstrate that PKD is essential for normal embryonic development and survival in mice, and that distinct PKD isoforms exhibit functional redundancy during this process.