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Biomedical subjects

M F Lyon

Publications and source records attributed to M F Lyon.

At least 73 records · Page 4Linked to original sources
PubMed1988

Experimental work on induced mutations.

The detection of changes in mutation rate in human populations remains extremely difficult. Thus estimation of genetic hazards of mutagens to man depends on extrapolation from experimental systems. Germ cells of animals show complex variations in sensitivity to mutagenic effects. Some agents predominantly affect stem cells or other immature germ cells, whereas others mainly affect later germ cell stages. Dose-response relations also vary both with the agent and with the stage or sex of germ cell treated. In man, in addition to single-gene defects and chromosome anomalies, conditions of complex or uncertain inheritance, such as congenital malformations, are clinically important. Genetic theory leaves unclear whether the incidence of these would be affected by a change in mutation rate. Recent research has shown that in mice the incidence of malformations is increased by exposure of the parents to mutagens, but the effect is small. Chromosomal non-disjunction is also clinically important. Again, recent research shows that its frequency can be changed by mutagens, but the effects vary with germ-cell stage. Thus, further research is needed to elucidate the relative contributions of different environmental mutagens to human genetic disease.

Abnormalities, Radiation-Induced↗
PubMed1988

Extent of the mouse t complex and its inversions shown by in situ hybridization.

Probes for loci situated near one end of the proximal (Tcp-1) and distal (Qa-2, 3) inversions of the mouse t complex have been hybridized to chromosomes of mice with and without t complexes and with morphologically distinguishable chromosome 17s. Both the probe for Tcp-1 and that for Qa-2, 3 hybridized to clearly different positions on t and non-t chromosomes, thus making visible the extent of the two inversions. The proximal inversion extends from roughly the junction of bands A1 and A2 to band A3, and the distal inversion from band A3 to band C. Thus, the whole t complex extends from the band A1-A2 junction to band C, and is therefore somewhat larger than previously thought, and occupies about 1.2% of the genome. A probe for complement component 3 (C3-1), genetically known to be several cM distal to the t complex, was found by in situ hybridization to lie in band E1. The proximal part of chromosome 17 is one of the best known parts of the mouse genome, at both the genetic and molecular levels. It may soon be possible to correlate the length of the t complex in terms of chromosomal distance with its physical length in megabases.

Animals↗
PubMed1988

Induction of congenital malformation in mice by parental irradiation: transmission to later generations.

In order to investigate the genetic basis of the increased incidence of congenital malformations in the offspring of irradiated mice, the frequency of malformations among the offspring of individual F1 sons of irradiated females was studied in detail. Among 90 fully tested F1 sons of females which had been mated 15-21 days after receiving 360 cGy X-rays 4 were definite or probable carriers of dominant genes giving a low penetrance of malformations. This confirms that the malformations seen in the first generation are of genetic origin and can be transmitted to later generations. However, the incidence and penetrance of the mutant genes detected were too low to account for all the anomalies found in the first generation. It was concluded that the genetic basis of the original anomalies was heterogeneous, with some due to genetic changes of high penetrance and rapidly eliminated, and others due to genes of low penetrance like those found in this work. Other malformations, in both the irradiated and control series, were probably of non-genetic origin.

Abnormalities, Radiation-Induced↗
PubMed1988

Localization of the human X-linked gene for chronic granulomatous disease to the mouse X chromosome: implications for X-chromosome evolution.

The gene encoded at the human X-linked chronic granulomatous disease locus (cytochrome b245 beta subunit) has been mapped to the mouse X chromosome using an interspecific Mus domesticus x M. spretus cross. The localization of this gene provides detailed information on one of the proposed ancestral breakpoints that account for the divergent evolution of the mouse and human X chromosomes.

Animals↗
PubMed1987

Construction of a detailed molecular map of the mouse X chromosome by microcloning and interspecific crosses.

A large number of microclones obtained by microdissection of the mouse X chromosome have been mapped using an interspecific Mus domesticus/Mus spretus cross. Clones displaying close linkage to a number of loci of known phenotype but unknown gene product, such as mdx (X-linked muscular dystrophy), have been obtained. Over a central 30 cM span of the mouse X chromosome, 17 clones have been mapped and ordered at a sufficient density to contemplate the complete physical mapping of this region that will aid in the isolation of a number of unidentified genes. Some of the mapped microclones detect moderately repetitive sequences that were clustered in several discrete regions of the mouse X chromosome.

Animals↗
PubMed1987

Chromosome maps of man and mouse, III.

Data on loci whose positions are known in both man and mouse are presented in the form of chromosomal displays, a table, and autosomal and X-chromosomal grids. At least 40 conserved autosomal segments with two or more loci, as well as 17 homologous X-linked loci, are now known in the two species, in which mitochondrial DNA is also highly conserved. Apart from the Y, the only chromosome now lacking a conserved group is human 13. Human 17 has a single conserved group which includes both short and long arms, and so may have remained largely intact in mammalian evolution. Human and mouse chromosomal maps show the approximate locations of homologous genes while the mouse map also shows the positions of translocations used in gene location.

Animals↗
PubMed1987

Localization of the Hprt locus by in situ hybridization and distribution of loci on the mouse X-chromosome.

The hypoxanthine phosphoribosyltransferase locus (Hprt) of the mouse has been localized by in situ hybridization to band XA6. Comparison of the distributions of known loci on the genetic and cytogenetic maps of the X-chromosome suggests some chiasma localization with a relatively high frequency of chiasmata in the F bands. In the A bands there appear to be fewer known loci than expected, but no evidence has been found so far of excessive chiasma formation.

Animals↗
PubMed1986

Male sterility of the mouse t-complex is due to homozygosity of the distorter genes.

Evidence is presented that the male sterility produced by the mouse t-complex is due to interaction of at least three sterility factors. These factors are carried in the same partial haplotypes as the three distorter genes, Tcd-1, Tcd-2, and Tcd-3 and are suggested to be identical with them. When heterozygous, the distorter/sterility genes act on the wild-type form of the responder gene, rendering sperm carrying it nonfunctional, thus leading to high transmission of the t form of the responder. When homozygous, the harmful effects of the distorter genes are stronger and affect both forms of the responder, leading to sterility. If homozygous sterility is an inescapable part of ratio distortion, then the t-lethals confer a selective advantage in removing sterile males from the population. Thus, the relationship between the various properties of the t-complex can now be understood.

Animals↗
PubMed1986

Long-term storage of eight-cell mouse embryos at - 196 degrees C.

Stocks of mutant mice have been reestablished from eight-cell embryos stored in liquid nitrogen for varying periods up to 11 years, and no evidence has been found of deterioration of survival with time of storage. Also, studies on the simulated cumulative effect of background radiation during storage failed to find any detrimental effect when embryos were exposed to the equivalent of about 2000 years of background radiation. However, in some cases embryos that carry mutant genes or chromosome anomalies tend to survive the freezing and thawing procedure less well than F1 hybrid embryos. Although this effect is probably independent of storage time, recent improvements in technique upon embryonic survival are to be welcomed.

Animals↗
PubMed1986

The Gy mutation: another cause of X-linked hypophosphatemia in mouse.

An X-linked dominant mutation (gyro, gene symbol Gy) in the laboratory mouse causes hypophosphatemia, rickets/osteomalacia, circling behavior, inner ear abnormalities, and sterility in males and a milder phenotype in females. Gy maps closely (crossover value 0.4-0.8%) to another X-linked gene (Hyp) that also causes hypophosphatemia in the mouse. Gy and Hyp genes have similar quantitative expression in serum phosphorus values, renal excretion of phosphate, and impairment of Na+/phosphate cotransport by renal brush-border membrane vesicles. These findings indicate that independent translation products of two X-linked genes serve phosphate transport in mouse kidney and thereby control phosphate content of extracellular fluid. The Gy translation product, unlike the Hyp product, is also expressed in the inner ear. These findings have implications for our understanding of the human counterpart known as "X-linked hypophosphatemia."

Alkaline Phosphatase↗
PubMed1986

Lack of inactivation of a mouse X-linked gene physically separated from the inactivation centre.

Previous evidence had shown that, when a mammalian X-chromosome is broken by a translocation, only one of the two X-chromosome segments shows cytological signs of X-inactivation in the form of late replication or Kanda staining. In the two mouse X-autosome translocations T(X;4)37H and T(X;11)38H the X-chromosome break is in the A1-A2 bands; in both, the shorter translocation product fails to exhibit Kanda staining. By in situ hybridization, the locus of ornithine carbamoyltransferase (OCT) was shown to be proximal to the breakpoint (i.e. on the short product) in T37H and distal to the breakpoint in T38H. Histochemical staining for OCT showed that in T38H the locus of OCT undergoes random inactivation, as in a chromosomally normal animal, whereas in T37H the OCT locus remains active in all cells. The interpretation is that, when a segment of X-chromosome is physically separated from the X-inactivation centre, it fails to undergo inactivation. This point is important for the understanding of the mechanism of X-inactivation, since it implies that inactivation is a positive process, brought about by some event that travels along the chromosome. It is also relevant to the interpretation of the harmful effects of X-autosome translocations and the abnormalities seen in individuals carrying such translocations.

Animals↗