ABSENCE OF YOLK-SAC HEMATOPOIESIS FROM MICE WITH A TARGETED DISRUPTION OF THE SCL GENE

The scl gene encodes a basic-helix-loop-helix transcription factor whi ch was identified through its involvement in chromosomal translocation s in T-cell leukemia. To elucidate its physiological role, scl was tar geted in embryonic stem cells. Mice heterozygous for the scl null muta tion were intercrossed and their offspring were genotyped. Homozygous mutant (scl(-/-)) pups were not detected in newborn litters, and analy sis at earlier time points demonstrated that scl(-/-) embryos were dyi ng around embryonic day 9.5. The scl(-/-) embryos were pale, edematous , and markedly growth retarded after embryonic day 8.75. Histological studies showed complete absence of recognizable hematopoiesis in the y olk sac of these embryos. Early organogenesis appeared to be otherwise normal. Culture of yolk sac cells of wild-type, heterozygous, and hom ozygous littermates confirmed the absence of hematopoietic cells in sc l(-/-) yolk sacs. Reverse transcription PCR was used to examine the tr anscripts of several genes implicated in early hematopoiesis. Transcri pts of GATA-1 and PU.1 transcription factors were absent from RNA from scl(-/-) yolk sacs and embryos. These results implicate scl as a cruc ial regulator of early hematopoeisis.