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Biomedical subjects

B R Migeon

Publications and source records attributed to B R Migeon.

122 records · Page 7Linked to original sources
PubMed1968

Human-mouse somatic cell hybrids with single human chromosome (group E): link with thymidine kinase activity.

Mouse somatic cells lacking thymidine kinase were mixed in culture with human diploid cells lacking hypoxanthine guanine phosphoribosyl transferase, and hybrid cells were isolated and maintained in a selective medium containing hypoxanthine, aminopterin, and thymidine. The hybrid cells at the time of isolation had karyotypes consisting predominantly of mouse chromosomes but with one human chromosome, a submetacentric member of group E, apparently giving thymidine kinase to the hybrid cell. However, after long-term propagation in the selective medium this chromosome has been lost, although cells continue to show thymidine kinase activity as demonstrated by the incorporation of (3)H-thy-midine into DNA in the hybrid cell. The hybrid cells have only mouse electro-phoretic variants for glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase, suggesting that the human genetic loci for these enzymes are not represented in the hybrid genome and may be unlinked to that for thymidine kinase.

Aminopterin↗
PubMed1968

Interferon production and action in mouse, hamster and somatic hybrid mouse-hamster cells.

A hybrid mouse-hamster cell line was developed from a mouse cell line which produces a high titer of interferon and is sensitive to its action, and a hamster cell line which produces little interferon and is relatively insensitive to its action. Parental cell lines demonstrated complete species specificity with respect to interferon production and action. The hybrid cells produced interferon (or interferons) effective when tested on the mouse cell line and primary hamster cells; the hybrids were sensitive to the action of both mouse and hamster interferons. Hybrid cells produced ten times more hamster interferon than the parent hamster cell line and were eight times more sensitive to hamster interferon than the parent hamster cell line.

Animals↗
PubMed1968

X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations.

Clones of skin fibroblasts cultured from the mother of two sons with X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch-Nyhan syndrome) were assayed for activity of this enzyme by measurement of the incorporation of (3)H-guanine into guanylic acid as counts per minute per microgram of protein and by autoradiography. The demonstration of two populations of clones, wild-type clones with normal enzyme activity and mutant clones unable to incorporate (3)H-guanine, is evidence that the locus for hypoxanthineguanine phosphoribosyl transferase on one of the X chromosomes is inactive.

Autoradiography↗
PubMedDate not supplied

Concerning the role of X-inactivation and DNA methylation in fragile X syndrome.

Elucidation of the role of DNA methylation in X chromosome inactivation along with recent studies of the fragile X mutation suggests that DNA methylation is likely to be a late event in the pathogenesis of the fragile X syndrome. Thus far, the evidence does not support suggestions that an impediment to X reactivation and failure to demethylate the inactive X in oocytes is responsible for silencing the fragile X. The role of DNA methylation is probably secondary to amplification of the CGG repeat to a critical size whether on active or inactive X. Further studies are needed to determine if late replication of the inactive X predisposes the locus on that chromosome to more extensive amplification.

DNA↗
PubMedDate not supplied

Second trimester prenatal diagnosis of epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome.

We report the second trimester prenatal echographic diagnosis of an epignathus teratoma in a female fetus with ring X chromosome mosaicism. The ring X chromosome mosaicism was present in the amniotic cell culture and in the teratoma and the ring X was inactive (X-inactive specific transcript (XIST) locus expressed). Hypoplastic left heart with valvular aortic stenosis and non-immune hydrops were additional findings, and are well-documented in Turner syndrome. The occurrence of epignathus teratoma in Turner syndrome has not been documented sofar.

Amniocentesis↗
PubMedDate not supplied

Insights into X chromosome inactivation from studies of species variation, DNA methylation and replication, and vice versa.

I am indebted to Mary Lyon as her X-inactivation hypothesis stimulated my mentor, Barton Childs, and in turn, myself, to think about the consequences of X-inactivation in heterozygous females. I often reread her original papers setting forth the single active X hypothesis, and still marvel at the concise and compelling exposition of the hypothesis and the logical predictions which seemed prophetic at my first reading, and have survived the test of time. My contribution to this Festschrift reviews evidence derived from studies of DNA methylation, species variation and DNA replication that reveals an important role for methylated CpG islands and suggests a role for late DNA replication in propagating X inactivation from one cell to its progeny. These studies also show that X inactivation is a powerful research tool for identifying the factors which program and maintain developmental processes.

Animals↗
PubMedDate not supplied

Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control elements of housekeeping genes.

DNA sequences of the X-chromosome-linked hypoxanthine phosphoribosyltransferase (HPRT) and glucose 6-phosphate dehydrogenase (G6PD) genes have revealed the presence of clusters of CpG dinucleotides, raising the possibility that such clusters are involved in the control of expression of these genes, which are expressed in all tissues. Although CpG clusters are not exclusive features of the X chromosome, the analysis of X-linked genes provides the means to determine whether CpG clusters are control elements; one of the two homologous X loci in female mammals is not expressed, so that active and inactive versions of the gene can be compared. In fact, it has been shown that these CpG clusters are undermethylated when the gene is active and extensively methylated when the gene is inactive. In addition to hypomethylation, chromatin hypersensitivity to endonuclease digestion is a known hallmark of regulatory sequences in eukaryotic genes. We report here that the CpG clusters of the active hprt and g6pd genes are not only undermethylated, but also hypersensitive to MspI, DNase I and S1 nuclease, further supporting the suggestion that they are involved in the control of expression of these genes.

Base Sequence↗
PubMedDate not supplied

Some insights into X chromosome inactivation from studies of human cells.

The inactivation of all but one X chromosome in the somatic cells of mammalian females in an important mechanism for regulating X chromosomal genes. Although the molecular basis for the single active X remains to be elucidated, recent studies have provided some insights. Inactivation occurs about the time of implantation, at least in mouse embryos. On the other hand, germ cells from human embryos have two active X chromosomes and may never be subjected to inactivation. As a consequence of X inactivation, one X chromosome becomes the sole determinant of X specified characteristics of the cell, resulting in cellular mosaicism. Transfer of gene products between cells occurs via gap junctions and by pinocytosis so that in heterozygotes carrying X linked mutations, the mutant phenotype may be masked by the presence of cells or normal type. There is considerable evidence that inactivation in the embryo is random with respect to parental origin of the X chromosome, but that selection occurs subsequently, and may lead to elimination of a whole population of cells in the female. Although there is evidence for preferential inactivation of the paternal X in extra-embryonic membranes of rodents, studies in human embryos have not been confirmatory. Analysis of clonal populations from heterozygotes for X chromosome mutations have been used to determine whether a whole X chromosome is inactive or only parts thereof. Individuals with multiple X chromosomes often manifest somatic abnormalities as well as gonadal ones. There is recent evidence that some loci on the short arm may escape inactivation. X inactivation in diploid human cells has been shown to be a very stable process. The silent X, once inactivated, maintains inactivity despite attempts to turn it on. Our recent studies of enzyme activity in cells from a human triploid abortus (69, XXY) with two active chromosomes indicates that the "active chromosomes" are also stably maintained. The presence of two active chromosomes in triploid cells implicates the autosomes in the regulation of X chromosome activity.

Animals↗