Double trans-chromosomic mice: Maintenance of two individual human chromosome fragments containing Ig heavy and κ loci and expression of fully human antibodies

摘要: The use of a human chromosome or its fragment as vector for animal transgenesis may facilitate functional studies large genomic regions. We describe here the generation and analysis double trans-chromosomic (Tc) mice harboring two individual fragments (hCFs). Two transmittable hCFs, one containing Ig heavy chain locus (IgH, ≈1.5 Mb) other κ light (Igκ, ≈2 Mb), were introduced into mouse strain whose endogenous IgH Igκ loci inactivated. In resultant double-Tc/double-knockout mice, substantial proportion somatic cells retained both rescue in defect production was shown by high level expression chains absence chains. addition, serum profiles four γ subclasses resembled those seen humans. They mounted an antigen-specific antibody response upon immunization with albumin, albumin-specific monoclonal antibodies various isotypes obtained from them. These results represent “humanized” using which suggest that Tc technology allow humanization over megabase-sized, complex animals. Such animals be useful not only studying vivo functions genome but also obtaining therapeutic products.