TARGETED DISRUPTION OF THE V-H 81X GENE - INFLUENCE ON THE B-CELL REPERTOIRE

We have generated a mutant mouse in which the most D-proximal V-H gene (V(H)81X) has been disrupted by introducing a neomycin-resistance gen e into the V(H)81X exon by means of gene targeting in embryonic stem c ells. The mutant mice generated are unable to express the V(H)81X gene but appear to display a normal pattern of B cell differentiation as w ell as normal numbers of bone marrow and peripheral B cells from fetal life all through ontogeny. They mount normal immune responses to seve ral different antigens tested. In contrast, the distribution of V-H ge ne rearrangements in the V(H)7183 family is altered in homozygous muta nt mice. Thus, the antibody repertoire of the targeted mice is modifie d, at least as far as the expression of V(H)7183 genes is concerned.