Molecular analyses of in vivo hprt mutations in human T-lymphocytes: IV. Studies in newborns.
In order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6-thioguanine resistant T-lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T-cells were studied to define hypoxanthine-guanine phosphoribosyltransferase (hprt) gene structural alterations and to determine T-cell receptor (TCR) gene rearrangement patterns. Structural hprt alterations, as shown by Southern blot analyses, occurred in 85% of these mutant clones. These alterations consisted mostly of deletion of exons 2 and 3. These findings contrast with the 10-20% of gross structural alterations (i.e., those visible on Southern blots) occurring randomly across the entire gene previously reported for T-cell mutants isolated from normal young adults. Iterative analyses of hprt structural alterations and TCR gene rearrangement patterns show that approximately one-third of the newborn derived mutants may have originated as pre- or intrathymic hprt mutations. This too contrasts with previous findings in adults where the background in vivo hprt mutations appeared to originate in postthymic T-lymphocytes.
McGinniss
M J
MJ
Department of Medicine, University of Vermont, Burlington.
Nicklas
J A
JA
Albertini
R J
RJ
D000328:Adult; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002999:Clone Cells; D015342:DNA Probes; D005312:Fetal Blood; D015329:Gene Rearrangement, T-Lymphocyte; D005796:Genes; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000032:analysis / Q000235:genetics*; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D013866:Thioguanine / Q000494:pharmacology
D015342:DNA Probes; D011948:Receptors, Antigen, T-Cell; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine