title: Phenotypical analysis of atypical PKCs in vivo function display a compensatory system at mouse embryonic day 7.5.
abstract: BACKGROUND
  The atypical protein kinases C (PKC) isoforms ι/λ and ζ play crucial roles in many cellular processes including development, cell proliferation, differentiation and cell survival. Possible redundancy between the two isoforms has always been an issue since most biochemical tools do not differentiate between the two proteins. Thus, much effort has been made during the last decades to characterize the functions of aPKCs using gene targeting approaches and depletion studies. However, little is known about the specific roles of each isoform in mouse development.
  
  
  RESULTS
  To evaluate the importance of PKCι in mouse development we designed PKCι deletion mutants using the gene targeting approach. We show that the deletion of PKCι, results in a reduced size of the amniotic cavity at E7.5 and impaired growth of the embryo at E8.5 with subsequent absorption of the embryo. Our data also indicate an impaired localization of ZO-1 and disorganized structure of the epithelial tissue in the embryo. Importantly, using electron microscopy, embryoid body formation and immunofluorescence analysis, we found, that in the absence of PKCι, tight junctions and apico-basal polarity were still established. Finally, our study points to a non-redundant PKCι function at E9.5, since expression of PKCζ is able to rescue the E7.5 phenotype, but could not prevent embryonic lethality at a later time-point (E9.5).
  
  
  CONCLUSIONS
  Our data show that PKCι is crucial for mouse embryogenesis but is dispensable for the establishment of polarity and tight junction formation. We present a compensatory function of PKCζ at E7.5, rescuing the phenotype. Furthermore, this study indicates at least one specific, yet unknown, PKCι function that cannot be compensated by the overexpression of PKCζ at E9.5.
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seidl
authors.forename: Ursula
authors.initials: U
authors.lastname: Braun
authors.forename: Norbert
authors.initials: N
authors.lastname: Roos
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.forename: Timo H-W
authors.initials: TH
authors.lastname: Lüdtke
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D058732:Embryoid Bodies / Q000166:cytology / Q000201:enzymology; D055786:Gene Knockout Techniques; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D010641:Phenotype; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta