Organization of the V Gene Segments in Mouse T-Cell Antigen Receptor α/δ Locus

The mouse T-cell receptor (TCR) α/δ locus was mapped using 17 Vα and 4 Vδ subfamily-specific probes. Four complementary methods were used: (1) an estimate of the V gene repertoire by Southern blot analysis of genomic DNA with subfamily-specific probes; (2) an analysis of V gene segments deleted by TCR gene rearrangements from a panel of T-cell tumors and hybridomas; (3) an analysis of overlapping clusters of cosmid clones; and (4) an analysis of large DNA fragments separated by field-inversion gel electrophoresis. The α/δ locus spans about 1 Mb. The distance between the 3′-most V gene segment (Vδ1) and the δ constant gene (Cδ) is no more than 150 kb. Sixty-six V gene segments have been mapped physically on cosmids. The members of individual Vα gene segment subfamilies are dispersed throughout the locus. In contrast, the Vδ gene segments Vδ1 to 5 are clustered at the 3′ end of the V gene segment cluster. At least two DNA segment duplications, 45 to 80 kb in length, are present in the locus. These data provide information on the evolution of the α/δ locus and on organizational features that might influence the expression of specific V gene segments in γδ cells.     

Distribution, metabolism, and fetal uptake of pentavalent arsenic in pregnant mice following oral or intraperitoneal administration

Pregnant CD-1 mice were treated with 20 (i.p.) or 40 (p.o.) mg/kg sodium arsenate on gestation day 18 (plug = day 1). Individual fetuses, pooled placentas and maternal blood, urine, liver, and kidneys were obtained from three or more litters at intervals up to 24 hours following treatment. Acid-digested samples were analyzed for total arsenic by hydride generation atomic absorption spectrophotometry. The rate of arsenic elimination from maternal samples was not influenced by administration route. First-order elimination followed a brief period of distribution, and the biological half-life was approximately 10 hours. Arsenic was found in most samples, with mean peak concentrations expressed as micrograms As/gm (wet wt.) or /ml (values listed are post-treatment sampling times in minutes or hours and concentrations for i.p. and for p.o. treated groups, respectively) as follows: fetuses-2, 3.5; 6, 0.8, placentas-2, 9.3; 1, 2.3, blood-10 minutes, 6.9; 1, 2.0, urine-1, 712; 2, 342, kidney-20 minutes, 25.4; 1, 11.0, liver-0.5, 7.9; 1, 11.7. By 24 hours, arsenic levels in fetuses and placentas had declined to 0.22 microgram/gm and 0.74 microgram/gm for i.p. and 0.33 microgram/gm and 0.57 microgram/gm for p.o. treatments, respectively. Fetal arsenic uptake and loss were more rapid following i.p. than p.o. treatments, and although the i.p. dose was only half that used p.o., peak fetal As+5 was almost fivefold higher following i.p. treatment. These results agree with the finding that oral dosing of pregnant mice with arsenate has less effect on the conceptus than does treatment by injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of porcine thyroid peroxidase and FAD-containing monooxygenase in the metabolism of 1-methyl-2-thioimidazole (methimazole)

The peroxidase and FAD-containing monooxygenase activities of porcine thyroid subcellular preparations were measured and it was observed that FAD-containing monooxygenase activity was considerably lower than that of peroxidase. The end product of 1-methyl-2[14C]thioimidazole oxidation catalysed by thyroid peroxidase was confirmed to be 1-methylimidazole by mass spectrometry. In the presence of thyroid peroxidase 1-methyl-2-thioimidazole would appear initially to be oxidised to bis(1-methylimidazole)-2,2'-disulphide. The extent of oxidation was dependent on the iodide concentration in the reaction mixture.     

Structural analysis of the mouse T-cell receptor Tcra V2 subfamily

Cosmid clones containing T-cell receptor Tcra V2 subfamily gene segments have been isolated from a BALB/c cosmid library and subjected to DNA sequence analysis. The V gene segments in the Tcra V2 subfamily differ from each other by 3%–7% at the nucleotide level and 5%–16% at the amino acid level. T-cell receptor Tcra V2 gene segment polymorphisms have been identified in the B10.PL and PL/J mouse strains with a Tcra V2 subfamily-specific probe. These V gene segment polymorphisms may cause the differential Tcra V gene usage in induced experimental allergic encephalomyelitis between B10.PL and PL/J mice.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide database and have been assigned the accession numbers U04312 and U04622-U04626