Profilin I is essential for cell survival and cell division in early mousedevelopment

Profilins are thought to play a central role in the regulation of de novo a ctin assembly by preventing spontaneous actin polymerization through the bi nding of actin monomers, and the adding of monomeric actin to the barbed ac tin-filament ends. Other cellular functions of profilin in membrane traffic king and lipid based signaling are also likely. Binding of profilins to sig naling molecules such as Arp2/3 complex, Mena, VASP, N-WASP, dynamin I, and others, further implicates profilin and actin as regulators of diverse mot ile activities. In mouse, two profilins are expressed from two distinct gen es. Profilin I is expressed at high levels in all tissues and throughout de velopment, whereas profilin II is expressed in neuronal cells. To examine t he function of profilin I in vivo, we generated a null profilin I (pfn1(ko) ) allele in mice. Homozygous pfn1(ko/ko) mice are not viable. Pfn1(ko/ko) e mbryos died as early as the two-cell stage, and no pfn1(ko/ko) blastocysts were detectable. Adult pfn1(ko/wt) mice show a 50% reduction in profilin I expression with no apparent impairment of cell function. However, pfn1(ko/w t) embryos have reduced survival during embryogenesis compared with wild ty pe. Although weakly expressed in early embryos, profilin Il cannot compensa te for lack of profilin I. Our results indicate that mouse profilin I is an essential protein that has dosage-dependent effects on cell division and s urvival during embryogenesis.