Mouse IgA allotypes have major differences in their hinge regions

Abstract

Six IgA allotypes are serologically identifiable in inbred mice. The sequences of the PCR-amplified C α 1, C α 2 and C α 3 exons from the genomic DNA of mice of four previously unsequenced allotypes already have been compared with those of BALB/c and of a wild mouse, Mus pahari, in the literature. Sporadic differences, including several that may encode the known allotypic determinants, are found throughout the three exons, but major differences occur in the hinge. The hinge is longest in DBA/2 (Igh-2 ^c) mice, having an extra codon compared with that of BALB/c (Igh-2 ^a) and B10.A (Igh-2 ^b) mice. It is two codons shorter in CE (Igh-2 ^f) and four shorter in M. pahari, AKR and NZB (both Igh-2 ^d) mice, but the position of the missing codons in the latter two strains is offset from that in M. pahari. The hinges in BALB/c (Igh-2 ^a) and DBA/2 (Igh-2 ^c) differ most from each other and from the other three allotypes, which are fairly closely related. Both BALB/c and DBA/2 have O-linked glycosylation sites, but they are in different positions in the hinge. Compared with BALB/c (Igh-2 ^a), B10.A(Igh-2 ^b) has two extra Cys residues in the hinge, while DBA/2 (Igh-2 ^c), AKR/NZB (Igh-2 ^d) and CE (Igh-2 ^f) each have one. The differences in hinge length may have arisen by mismatching of highly repetitive portions of its sequence during meiotic recombination. Possible effects of the differences in hinge length and composition on the behavior of the mouse IgA allotypes are discussed.