MICE CARRYING A CD20 GENE DISRUPTION

CD20 is a hallmark antigen of B lymphocytes. Its expression is restric ted to precursor and mature B cells but it is not expressed on plasma cells. The protein is a membrane-embedded phosphoprotein that appears likely to transverse the membrane four times. Its function is unknown although CD20 has been variously proposed to play a role in B-cell act ivation, proliferation, and calcium transport. A unique homologue of h uman CD20 has been described in mouse, which also shows a B-cell-speci fic pattern of expression. Here we describe the generating of mice car rying a CD20 gene disruption. So far, we have failed to detect any maj or effect of the gene disruption on the differentiation and function o f B lymphocytes as judged by the expression of surface markers, antige n receptor signaling, proliferative responses, or calcium uptake. We d id note, however, that the mice homozygous for the gene disruption [ge nerated by intercrossing (129 X C57BL/6)F-1 CD20(+/-) heterozygotes] s howed a substantial depletion of the sub-population of peritoneal B ce lls that lack expression of the B220 (RA3-6B2) isoform of CD45. The lo ss of the IgM(+) 6B2(-) peritoneal B cells is not, however, attributab le to the CD20 gene disruption itself. Rather, it segregates with a po lymorphic difference between the 129 and C57BL/6 strains that is linke d to the CD20 locus which, intriguingly, is itself close to the CD5 ge ne. This demonstrates that caution must be exercised when comparing th e phenotypes of F-2 litter-mates generated from crosses between 129 em bryonic stem-cell-derived chimeras and mice of other strains.