Further evidence that BALB/c and C57BL/6 gamma 2a genes originate from two distinct isotypes

Gene conversion by the corresponding gamma 2b gene has been proposed to explain the multiple differences between the nucleic acid sequences of BALB/c (Igh-1a) and C57BL/6 (Igh-1b) gamma 2a immunoglobulin allelic genes. However, genetic analysis indicates that duplicated forms of gamma 2a genes are not only present in Eastern Asia, but also in European wild mouse populations which suggests a widespread phenomenon. In order to verify whether the gamma 2a-related isotypic genes, namely gamma 2c and gamma 2a, could correspond to those present as alleles in domestic mice (Igh-1b and Igh-1a), a genomic library from Mus m.musculus strain (MAI) was constructed. Extensive mapping of the recombinant phages and Southern blot analysis with several restriction enzymes gave the complete organization of these loci: gamma 2b (18 kb) gamma 2c (17 kb) gamma 2a (14 kb) epsilon. The homology in flanking, coding and intervening region sequences indicates that MAI gamma 2c and gamma 2a related genes correspond to C57BL/6 and BALB/c Igh-1 alleles respectively. Also, Southern blot analysis using several probes derived from exonic and intronic regions between gamma 2b and gamma 2a genes shows a 2.0- to 3.0-kb difference in the distance between gamma 2b and gamma 2a genes of BALB/c strain as compared to C57BL/6. Taken together, these results indicate that BALB/c and C57BL/6 gamma 2a genes could originate from different isotypes.