Evolutionary relationships and polymorphisms among V kappa 10 genes from inbred and wild-derived inbred mice.
The V kappa 10 family in BALB/c mice is composed of three members, two of which are utilized in a variety of immune responses. We previously demonstrated that the product of the third gene, V kappa 10C, has never been detected as part of a functional antibody and productive rearrangements are selectively lost during B-cell development. Here we analyzed germline V kappa 10 genes from inbred and wild-derived mice by RFLP and sequencing in order to determine the origin of the V kappa 10C gene, as well as to examine the evolutionary relationships of V kappa 10 genes. Our results demonstrated that the V kappa 10 family is highly conserved across Mus species and subspecies, but that V kappa 10C is rare, being found in only inbred mice of V kappa 10 allelic group b and two of six M. m. domesticus isolates. It was not found in other M. musculus subspecies or M. spretus. V kappa 10A and V kappa 10B were found in all strains, with the exception of one M. m. domesticus isolate, which had only V kappa 10B genes. Overall, V kappa 10A sequences were more highly conserved than V kappa 10B, indicating that different selective pressures may be operating on these genes. The two V kappa 10C sequences from M. m. domesticus were 100% identical to that found in inbred mice. V kappa 10C is more closely related to V kappa 10B than to V kappa 10A and our data suggest that it is a recent duplication of the V kappa 10B gene.
Fitzsimmons
Sean P
SP
Center for Biologics Evaluation and Research, Division of Monoclonal Antibodies, Food and Drug Administration, 1401 Rockville Pike HFM-561, Rockville, MD 20852-1448, USA.
Clark
Kathleen J
KJ
Shapiro
Marjorie A
MA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D015139:Blotting, Southern; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains