Sequence and structure of the mouse ThB gene.
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Amino Acid Sequence↗
Biomedical subjects
T P Gumley
Publications and source records attributed to T P Gumley.
Tissue expression, structure and function of the murine Ly-6 family of molecules.
Murine Ly-6 molecules are a family of cell surface glycoproteins which have interesting patterns of tissue expression during haematopoiesis from multipotential stem cells to lineage committed precursor cells, and on specific leucocyte subpopulations in the peripheral lymphoid tissues. These interesting patterns of tissue expression suggest an intimate association between the regulation of Ly-6 expression and the development and homeostasis of the immune system. Ly-6 molecules are low molecular weight phosphatidyl inositol anchored glycoproteins with remarkable amino acid homology throughout a distinctive cysteine rich protein domain that is associated predominantly with O-linked carbohydrate. These molecules are encoded by multiple tightly linked genes located on Chr. 15 which have conserved geneomic organization. The in vivo functions of Ly-6 molecules are not known although in vitro studies suggest a role in cellular activation. This review will summarize our understanding of Ly-6 with regard to tissue expression, molecular structure, gene organization and function.
Amino Acid Sequence↗
Polymorphism at the mouse Thb locus.
Mouse ThB is a 15,000 M(r) glycosyl phosphatidyl inositol anchored cell surface glycoprotein that shares amino acid homology with Ly-6 molecules; the gene is closely linked to Ly-6 on chromosome 15. The Thb locus has two alleles, Thbh and Thbl, which control the level of expression of ThB molecules on thymocytes (as shown herein) and on splenic B cells, and is therefore different from the usual polymorphisms of other Ly loci which give an all or none serological reaction. The reason for the expression polymorphism is unknown and could include a different protein structure in ThB molecules, altered glycosylation, or differences in transcriptional control. To determine the reason for the differences in expression, we examined the RNA (cDNA) sequence of Thbh and Thbl alleles: there was complete nucleotide identity in the cDNA sequence in both ThB(high) (C57BL/6)- and ThB(low) (BALB/c)-expressing strains; the RNA and protein sequences would therefore be identical. In addition to the difference in the amount of cell surface glycoprotein, there was also a difference in the level of ThB mRNA in ThB(high) and ThB(low) strains; thus the differences in ThB expression are likely to be due to different rates of transcription of the two alleles.
Alleles↗
Isolation and characterization of cDNA clones for the mouse thymocyte B cell antigen (ThB).
The Thb locus is responsible for the expression of 15-kDa phosphatidyl inositol anchored molecules (ThB) on murine thymocytes and B cells. Thb expression as detected with mAb is polymorphic on B cells with two alleles, Thbh and Thb1 responsible for the high and low expression of ThB on B cells. The regulatory locus for Thb expression had been mapped with the Ly-6 cluster of genes to Chr 15. In our study we used expression cloning in COS cells to isolate cDNA clones that code for ThB after transfection; the cDNA products react with anti- ThB antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies. One of these clones, pThB-A contains insert of 702 bases which was sequenced. The translated amino acid sequence has 11 cysteine residues, and together with the absence of potential N-linked glycosylation sites is similar to the structure of the Ly-6 molecules. The nucleotide and amino acid sequences of ThB cDNA were compared to those of Ly-6 genes and the Ly-6 related human CD59 and show clear homology. Finally using interspecies crosses, the structural Thb gene has been mapped to Chr 15; thus both structural and regulatory genes map to a similar site. The genetic map location near Ly-6 and the sequence similarity suggest that Thb and Ly-6 may have been derived from the same progenitor by gene duplication.
Amino Acid Sequence↗
Isolation and characterization of cDNA clones for mouse Ly-9.
We describe the production and characterization of a mouse mAb, S-450-33.2, recognizing the Ly-9.2 specificity. This mAb was used to purify Ly-9 molecules from lymphoid cell lines, and the amino-terminal amino acids were determined. The mAb was also used in a eukaryotic expression system, to isolate cDNA clones encoding Ly-9. Analysis of RNA showed that Ly-9 expression is lymphocyte specific, as determined by the presence of a single hybridizing 2.4-kb species found only in lymphoid cells. Genomic DNA analysis indicated that Ly-9 is encoded by a single-copy gene of 10 to 15 kb. The predicted polypeptide belongs to the Ig superfamily of cell surface molecules with four extracellular Ig-like domains, i.e., a non-disulfide-bonded V domain, a truncated C2 domain with two disulfide bonds, a second non-disulfide-bonded V domain, and a truncated C2 domain with two disulfide bonds (V-C2-V-C2). The sequence data also support the view that Ly-9 belongs to the subgroup of the Ig superfamily that includes Bcm-1, CD2, and LFA-3.
Amino Acid Sequence↗