Targeted disruption of the murine Plag1 proto-oncogene causes growth retardation and reduced fertility.
The pleomorphic adenoma gene 1 (Plag1) proto-oncogene encodes a transcription factor and is implicated in human tumorigenesis via ectopic overexpression. No information is available about its developmental role. To address this, a Plag1-/- mouse strain was generated and it appears that Plag1-deficient mice are viable. No anatomical differences are obvious at birth, except that the weight of Plag1-/- mice is significantly lower in comparison to control litter mates. This early growth retardation is maintained throughout adult life with proportionally smaller organs except for the disproportionally small seminal vesicles and ventral prostate; however, plasma testosterone levels in males were not affected. Furthermore, fertility of both male and female Plag1-/- is reduced. Northern blot analysis revealed that Plag1 is developmentally regulated with high overall fetal expression levels, which drop after birth. Furthermore, Plag1 is differentially expressed and is readily detectable in the reproductive organs and pituitary. Expression of growth regulatory Igf2, a known target gene of Plag1 in tumorigenesis, was not affected in Plag1-/- embryos and pups. The general morphology and histology of the size-reduced pituitaries was not affected. Our results establish that Plag1 disruption in mouse differentially affects pre- and postnatal growth and development of organs, with reproductive repercussions.
Hensen
Karen
K
Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology (VIB), Herestraat 49, B-3000 Leuven, Belgium.
Braem
Caroline
C
Declercq
Jeroen
J
Van Dyck
Frederik
F
Dewerchin
Mieke
M
Fiette
Laurence
L
Denef
Carl
C
Van de Ven
Wim J M
WJ
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics; D005298:Fertility / Q000235:genetics*; D006128:Growth / Q000235:genetics*; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010903:Pituitary Gland, Anterior / Q000196:embryology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas
D017931:DNA Primers; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C491264:Plag1 protein, mouse; D000090063:Proto-Oncogene Mas; D007335:Insulin-Like Growth Factor II