G7c in the lung tumor susceptibility (Lts) region of the Mhc class III region encodes a von Willebrand factor type A domain protein

• Published in: Immunogenetics (New York) 2001-02, Vol.53 (1), p.64-68
• Main Authors: Kumánovics, A, Lindahl, K F
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Databases as Topic; G7c gene; Genetic Predisposition to Disease; HLA Antigens - genetics; Humans; Lung Neoplasms - genetics; Major Histocompatibility Complex - genetics; Molecular Sequence Data; N-ethyl-N-nitrosourea; Phylogeny; Protein Structure, Tertiary; Sequence Alignment - methods; Sequence Homology, Amino Acid; von Willebrand Factor - genetics; von Willebrand factor type A domain protein
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s002510100297

Four susceptibility loci for experimentally induced disease, orchitis (Orch1), cleft palate (Cps1), hormonally induced mammary tumor, and chemically induced lung tumor (Lts), as well as the high-IgG2a phenotype (Igis1; Matthews et al. 2000) are mapped into the similar to 70-kb region of Hsc7O t-G7 in the mouse major histocompatibility complex (Mhc or H2). Experimental allergic orchitis is an organ-specific autoimmune disease that is induced in susceptible mouse strains by immunization with testis homogenate (Teuscher et al. 1990). An experimental model of nonsyndromic cleft palate is induced in susceptible fetal mice by injecting steroids (Gasser et al. 1988). Mammary tumors are induced using heterotopic hypophyseal isograft (Roepcke et al. 1990). Lung tumors are induced in susceptible mouse strains by prenatal N-ethyl-N-nitrosourea treatment. At least three regions within the Mhc contain lung tumor susceptibility loci. The locus influencing the alveolar, but not the papillary lung tumors was mapped between Hsp70.3 and G7 by H2 congenic, intra-H2 recombinant mice (Fijneman et al. 1995). The recombinational breakpoint between haplotypes susceptible and resistant for Lts has recently been mapped precisely into the G7c gene (Albertella et al. 1996; Snoek et al. 1998, 2000). This gene encodes a protein which has been reported as similar to hemicentin but nothing else (Snoek et al. 2000). Hemicentin (or F15G9.4) is a Caenorhabditis elegans protein in GenBank (gi: 7499208). The connection between lung tumors and G7c would be easier to make if one could assign a function to G7c, or at least place it in a functional category (e.g., translation, transcription, DNA for replication, cell motility, ion transport); we therefore reanalyzed the G7c protein sequence.