Wetsel R A, Kulics J, Lokki M L, Kiepiela P, Akama H, Johnson C A, Densen P, Colten H R
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 1996 Mar 8;271(10):5824-31. doi: 10.1074/jbc.271.10.5824.
Type II complement protein C2 deficiency is characterized by a selective block in C2 secretion. The Type II C2 null allele (C2Q0) is linked to two major histocompatibility haplotypes (MHC) that differ from the MHC of the more common Type I C2 deficiency. To determine the molecular basis of Type II deficiency the two Type II C2Q0 genes were isolated and transfected separately into L-cells. Subsequent molecular biology, biosynthetic, and immunofluorescence studies demonstrated that C2 secretion is impaired in Type II C2 deficiency because of different missense mutations at highly conserved residues in each of the C2Q0 alleles. One is in exon 5 (nucleotide C566 --> T; Ser189 --> Phe) of the C2Q0 gene linked to the MHC haplotype A11,B35,DRw1,BFS, C4A0B1. The other is in exon 11 (G1930 --> A; Gly444 --> Arg) of the C2Q0 gene linked to the MHC haplotype A2,B5, DRw4,BFS,C4A3B1. Each mutant C2 gene product is retained early in the secretory pathway. These mutants provide models for elucidating the C2 secretory pathway.
II型补体蛋白C2缺乏症的特征是C2分泌存在选择性阻断。II型C2无效等位基因（C2Q0）与两种主要组织相容性单倍型（MHC）相关联，这两种单倍型不同于更常见的I型C2缺乏症的MHC。为了确定II型缺乏症的分子基础，将两个II型C2Q0基因分离并分别转染到L细胞中。随后的分子生物学、生物合成和免疫荧光研究表明，II型C2缺乏症中C2分泌受损是由于每个C2Q0等位基因中高度保守残基处存在不同的错义突变。一个位于与MHC单倍型A11、B35、DRw1、BFS、C4A0B1相关联的C2Q0基因的外显子5（核苷酸C566→T；Ser189→Phe）。另一个位于与MHC单倍型A2、B5、DRw4、BFS、C4A3B1相关联的C2Q0基因的外显子11（G1930→A；Gly444→Arg）。每个突变型C2基因产物在分泌途径早期被滞留。这些突变体为阐明C2分泌途径提供了模型。
