E2F4 is essential for normal erythrocyte maturation and neonatal viability.
The retinoblastoma protein (pRB) plays a key role in the control of normal development and proliferation through the regulation of the E2F transcription factors. We generated a mutant mouse model to assess the in vivo role of the predominant E2F family member, E2F4. Remarkably, loss of E2F4 had no detectable effect on either cell cycle arrest or proliferation. However, E2F4 was essential for normal development. E2f4-/- mice died of an increased susceptibility to opportunistic infections that appeared to result from craniofacial defects. They also displayed a variety of erythroid abnormalities that arose from a cell autonomous defect in late stage maturation. This suggests that E2F4 makes a major contribution to the control of erythrocyte development by the pRB tumor suppressor.
Humbert
P O
PO
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Rogers
C
C
Ganiatsas
S
S
Landsberg
R L
RL
Trimarchi
J M
JM
Dandapani
S
S
Brugnara
C
C
Erdman
S
S
Schrenzel
M
M
Bronson
R T
RT
Lees
J A
JA
D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle; D002455:Cell Division; D019465:Craniofacial Abnormalities / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D004198:Disease Susceptibility; D050704:E2F4 Transcription Factor; D005314:Embryonic and Fetal Development / Q000235:genetics*; D004912:Erythrocytes / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009894:Opportunistic Infections / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D011994:Recombinant Proteins; D014157:Transcription Factors