Structure and chromosomal location of the gene encoding mouse corticosteroid-binding globulin: strain differences in coding sequence and steroid-binding activity.
Corticosteroid-binding globulin (CBG) is a member of the serine proteinase inhibitor superfamily and is responsible for the plasma transport of glucocorticoids. The mouse Cbg gene structure has been deduced from two non-overlapping DNA fragments of a lambda EMBL-3 genomic library, as well as PCR amplification of the approx. 2 kb of genomic DNA that lies between them. Mouse Cbg comprises five exons that span a region of approx. 10.5 kb, and has been localized in tight linkage with the Aat (alpha 1-antitrypsin) and Spi (serine proteinase inhibitor) gene complex on chromosome 12, in a region syntenic with this genetic locus on human chromosome 14. Intron-specific oligodeoxyribonucleotide primers were also used to PCR-amplify Cbg coding regions from several mouse strains. No differences were found in the Cbg coding sequences of BALB/c and C57BL/6J-cpk/cpk mice, while two mutations were found within RIIIS/J Cbg that result in Lys201-->Glu and Ala357-->Thr substitutions in the mature mouse CBG polypeptide. To assess what impact these substitutions might have on the steroid-binding activity of RIIIS/J CBG, these mutations were introduced separately or together into a BALB/c mouse Cbg cDNA. Expression of these mutants in the MDCK cell line indicated that the Lys201-->Glu substitution accounts for the abnormal steroid-binding affinity of CBG in RIIIS/J mice.
Orava
M
M
Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.
Zhao
X F
XF
Leiter
E
E
Hammond
G L
GL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D014156:Transcortin / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D014156:Transcortin