Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor.
We have cloned a partial cDNA encoding murine stem cell factor (SCF) and show that the gene is syntenic with the Sl locus on mouse chromosome 10. Using retroviral vectors to immortalize fetal liver stromal cell lines from mice harboring lethal mutations at the Sl locus (Sl/Sl), we have shown that SCF genomic sequences are deleted in these lines. Furthermore, two other mutations at Sl, Sld and Sl12H, are associated with deletions or alterations of SCF genomic sequences. In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice. We have also provided biological and physical evidence that SCF is a ligand for the c-kit receptor.
AMGEN Inc., AMGEN Center, Thousand Oaks, California 91320.
K M
KM
Zsebo
D A
DA
Williams
E N
EN
Geissler
V C
VC
Broudy
F H
FH
Martin
H L
HL
Atkins
R Y
RY
Hsu
N C
NC
Birkett
K H
KH
Okino
D C
DC
Murdock
D000595:Amino Acid Sequence; D000748:Anemia, Macrocytic / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005796:Genes; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D006822:Hybrid Cells / Q000166:cytology; D008024:Ligands; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D014162:Transfection
D016298:Hematopoietic Cell Growth Factors; D008024:Ligands; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit