| First Author | Hackenmiller R | Year | 2002 |
| Journal | Dev Biol | Volume | 245 |
| Issue | 2 | Pages | 255-69 |
| PubMed ID | 11977979 | Mgi Jnum | J:76509 |
| Mgi Id | MGI:2179608 | Doi | 10.1006/dbio.2002.0643 |
| Citation | Hackenmiller R, et al. (2002) Truncation of c-fes via gene targeting results in embryonic lethality and hyperproliferation of hematopoietic cells. Dev Biol 245(2):255-69 |
| abstractText | The c-fes protooncogene encodes a nonreceptor tyrosine kinase (Fes) implicated in cytokine receptor signal transduction, granulocyte survival, and myeloid differentiation. To study the role of c-fes during myelopoiesis, we generated embryonic stem (ES) cells with a targeted disruption of the c-fes locus. Targeted mutagenesis deletes the C-terminal SH2 and tyrosine kinase domains of c-fes (referred to as c-fes(Delta c/Delta c)). We demonstrate that the c-fes(Delta c/Delta c) allele results in a truncated Fes protein that retains the N-terminal oligomerization domain, but lacks both the SH2 and the tyrosine kinase domain. In vitro differentiation of c-fes(Delta c/Delta c) ES cells results in hyperproliferation of an early myeloid cell. Generation of c-fes(Delta c/Delta c) mutant chimeric mice causes lethality by E13.5 with embryos exhibiting pleiotropic defects, the most striking being cardiovascular abnormalities. These results establish that c-fes is an important regulator of myeloid cell proliferation and embryonic development. |
