The conserved phosphoinositide 3-kinase pathway determines heart size in mice.
Phosphoinositide 3-kinase (PI3K) has been shown to regulate cell and organ size in Drosophila, but the role of PI3K in vertebrates in vivo is not well understood. To examine the role of PI3K in intact mammalian tissue, we have created and characterized transgenic mice expressing constitutively active or dominant-negative mutants of PI3K in the heart. Cardiac- specific expression of constitutively active PI3K resulted in mice with larger hearts, while dominant-negative PI3K resulted in mice with smaller hearts. The increase or decrease in heart size was associated with comparable increase or decrease in myocyte size. Cardiomyopathic changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile dysfunction, were not observed in either of the transgenic mice. Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals.
Shioi
T
T
Cardiovascular Division, Beth Israel Deaconess Medical Center and Departments of Medicine and Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
Kang
P M
PM
Douglas
P S
PS
Hampe
J
J
Yballe
C M
CM
Lawitts
J
J
Cantley
L C
LC
Izumo
S
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D048429:Cell Size; D004452:Echocardiography; D004790:Enzyme Induction; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006321:Heart / Q000033:anatomy & histology*; D051379:Mice / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D016277:Ventricular Function, Left
D011993:Recombinant Fusion Proteins; D009320:Atrial Natriuretic Factor; D019869:Phosphatidylinositol 3-Kinases; D019893:Ribosomal Protein S6 Kinases; D018995:Myosin Heavy Chains