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Biomedical subjects

M F Lyon

Publications and source records attributed to M F Lyon.

At least 91 records · Page 5Linked to original sources
PubMed1986

Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse.

Small eyes (Sey) is a semidominant, homozygous lethal mutation in the mouse (Roberts, 1967). It is allelic with SeyH, a radiation-induced homozygous prenatal lethal which has been mapped on chromosome 2. The effect of the Sey mutation is apparently limited to the growth and differentiation of the presumptive lens and nasal placodes. Homozygous Sey/Sey embryos can be distinguished as early as 10.5 days post coitum (p.c.); the optic vesicles grow out, but the ectoderm does not give rise to a lens and nasal pits never form. Immunohistochemical studies show that the distribution of the extracellular matrix glycoprotein laminin is not significantly different in the cephalic region of Sey/Sey versus Sey/+ or +/+ embryos. Sey/Sey embryos develop to term but without eyes or nose, and die soon after birth. Further analysis of Sey/Sey embryos may throw light on the mechanisms underlying morphogenesis of craniofacial structures in mammals.

Animals↗
PubMed1985

Discrimination between the effects of X-ray irradiation of the mouse oocyte and uterus on the induction of dominant lethals and congenital anomalies.

In order to test whether irradiation of the postimplantation maternal environment had any effect on the apparent induction of dominant lethals or congenital anomalies by radiation, preimplantation embryos were surgically transferred between females which had been irradiated before conception or left untreated. A high proportion of preimplantation embryos, collected from females that had been irradiated 15-21 days prior to conception with 3.6 Gy X-rays, were either arrested or developmentally retarded compared with those collected from untreated females. The transfer experiments indicate that irradiation of the uterus has no significant effect on the frequency of subsequent postimplantation mortality or on mean fetal weight. However, it remains unclear whether irradiation of the uterus contributes to the induction of congenital anomalies.

Animals↗
PubMed1985

Discrimination between the effects of X-ray irradiation of the mouse oocyte and uterus on the induction of dominant lethals and congenital anomalies. II. Localised irradiation experiments.

In order to evaluate whether irradiation of the postimplantation maternal environment contributed to the induction of postimplantation mortality or congenital anomalies, mouse ovaries were surgically exteriorised and selectively irradiated or shielded in a specially constructed apparatus. The results show that exposure of the mouse abdomen and uterus to 3.70 Gy X-rays, 15-21 days prior to conception, has no significant effect on the incidence of either postimplantation mortality or congenital anomalies. Exposure of the ovaries to 3.27 Gy X-rays during the same period, however, increased the frequency of both postimplantation mortality and congenital anomalies.

Animals↗
PubMed1985

Molecular probes define different regions of the mouse t complex.

Four genomic clones obtained from microdissected fragments of the proximal portion of mouse chromosome 17 have been used to identify a series of t-haplotype-specific restriction fragments. Their specificity is defined by presence in eight complete t haplotypes and absence from 18 inbred strains of wild-type mice. Partial t haplotypes contain subsets of the t-specific fragments, and each can be classified according to the t-specific fragments it contains. This is the first molecular evidence that independent partial t haplotypes contain different lengths of t haplotype DNA. Recombination studies indicate that partial t haplotypes suppress recombination in proportion to the extent of t haplotype DNA they contain. Molecular analysis of partial t haplotypes shows that the t-specific fragments map to and thus define different regions of the t complex. Certain regions of t haplotype DNA defined by t-specific restriction fragments can be correlated with loci involved in the control of transmission ratio distortion.

Alleles↗
PubMed1985

The gene triplet Rw W Ph controls murine haematopoiesis.

Having shown a haematopoietic role for Patch (Ph), especially when doubly heterozygous with the mutant Wct (Loutit & Cattanach, 1983) we have similarly examined the Rw locus, the third member of the triplet. Mature Rw/+mice have a just detectable macrocytic anaemia. When doubly heterozygous with Wct and Wv the mild anaemia of these W mutants is exaggerated but with W19H (not anaemic as single heterozygote) red cell factors are as for Rw/+. Rw/+mice are strikingly more sensitive to the lethal effects of X-irradiation (MLD 6.66 +/- 0.10 Gy) on haematopoiesis than comparable +/+ mice (MLD 8 Gy). Those mice that do recover after X-irradiation do not exhibit the delay in recovery of erythropoiesis that is evident with characteristic W mutants in both single and double dose. Furthermore the double heterozygote Wct+/+Rw has a significantly lower MLD (5.19 +/- 0.17 Gy) for X-radiation than Wct/+ (MLD 6.48 +/- 0.24 Gy). We argue that all three loci W, Ph and Rw, influence haematopoietic stem cells, leading to increased radiosensitivity when deletions or mutant genes are present.

Anemia, Macrocytic↗
PubMed1985

The arrangement of H-2 class I genes in mouse t haplotypes.

The t haplotypes of mouse chromosome 17 bear a number of interesting mutations and rearrangements, some of which map close to the H-2 complex. Since there are many H-2 class I genes of unknown function, we have investigated their arrangement in t haplotypes using genomic Southern blots. We present a detailed chart of the H-2w30 (tw12) complex, and compare it with the arrangement in other t haplotypes and standard mouse haplotypes. The chart shows duplications, deletions, and reshuffling of conserved and divergent regions. The two major features of the t arrangement--large deletions in the Qa and Tla regions--have analogues in some standard strains, so it is unlikely that these deletions are responsible for t-specific phenotypes. The differences between t and standard mouse strains are similar, in nature and in degree, to those between different standard strains.

Alleles↗
PubMed1985

Clonal analysis of X-chromosome inactivation and the origin of the germ line in the mouse embryo.

Cloning of cells from peri-implantation embryos by blastocyst injection was used to investigate the time of X-chromosome inactivation in that part of the ectoderm lineage giving rise to foetal tissues of the mouse. Matings were arranged so that the two X-chromosomes of female donor cells controlled two distinct coat colours and host blastocysts were of a third colour genotype. No coat chimaeras were obtained in experiments using donor cells from the primitive ectoderm of 6th or 7th day embryos or from lactationally delayed implanting or reactivated blastocysts. In contrast, a minimum of 80 unequivocal coat chimaeras were obtained in experiments in which primitive ectoderm cells from 5th day implanting blastocysts were used for injection. The majority of these chimaeras that had received a female cell exhibited both donor colours in addition to host colour in their coats, suggesting that the donor cell had not undergone X-inactivation until one or more cycles after transplantation. The remainder of such chimaeras exhibited only one or other donor coat colour. Determination of the parental origin of the allocyclic X-chromosome in donor metaphase preparations in internal tissues of several chimaeras revealed that the coat pattern did not always reflect the X-activity status of the donor cell clone as a whole. Nevertheless, the findings suggest that X-inactivation takes place shortly after implantation in the primitive ectoderm cell population from which the foetus is derived. Of the 68 chimaeras in which the sex of both the donor and host component was established 62 proved to be fertile. Furthermore, 21 of the 37 fertile chimaeras whose sex corresponded with that of the donor cell yielded functional gametes of donor origin. Injection of cells from a single donor blastocyst into a series of host blastocysts established that at least 2 cells in 5th day primitive ectoderm can give rise to both somatic cells and functional germ cells among their mitotic descendants.

Animals↗
PubMed1984

Analysis of male sterile mutations in the mouse using haploid stage expressed cDNA probes.

A differential hybridization screening procedure has identified cDNAs which correspond to RNAs which are expressed in mouse testis and at lower levels in liver and spleen. The sensitivity of this procedure is such that approximately 0.5% of 1.4 X 10(4) cDNA clones are revealed as "testis specific". We have focused on ten cDNA clones which have been used to identify RNAs expressed in the haploid phase of spermatogenesis. Using Northern blots to analyse RNA isolated from the testes of mutant mice (Tfm/Y and Sxr/+) blocked at specific stages in spermatogenesis or RNA from sexually immature mice, 8 clones have been identified which correspond to RNAs expressed uniquely or at much higher levels in meiotic or post meiotic cells.

Animals↗
PubMed1984

Induction of congenital malformations in the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages.

The induction of congenital malformations among the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages has been studied in two experiments. Firstly, animals were exposed to varying doses (108-504 cGy) of X-rays and mated at various time intervals (1-7, 8-14, 15-21 and 64-80 days post-irradiation), so as to sample spermatozoa, spermatids and spermatogonial stem cells. In the second experiment, only treated spermatogonial stem cells were sampled. One group of males was given a single 500-cGy dose, a second group a fractionated dose (500 + 500 cGy, 24 h apart) and a third group was left unexposed. In the first experiment, induced post-implantation dominant lethality increased with dose, and was highest in week 3, in line with the known greater radiosensitivity of the early spermatid stage. Preimplantation loss also increased with dose and was highest in week 3. There was no clear induction of either pre-implantation or post-implantation loss at spermatogonial stem cell stages. There was a clear induction of congenital malformations at post-meiotic stages, the overall incidence being 2.0 +/- 0.32% in the irradiated series and 0.24 +/- 0.17% among the controls. The induction was statistically significant at each dose. At the two highest doses the early spermatids (15-21 days) appeared more sensitive than spermatozoa, and at this stage the incidence of malformations increased with dose. The data from Expt. 1 on the induction of malformations by irradiation of spermatogonial stages were equivocal. In contrast, Expt. 2 showed a statistically significant induction of malformations at both dose levels (2.2 +/- 0.46% after 500 cGy and 3.1 +/- 0.57% after 500 + 500 cGy). The relative sensitivities of male stem cells, post-meiotic stages and mature oocytes to the induction of congenital malformations were reasonably similar to their sensitivities for specific-locus mutations, except that the expected enhancing effect of the fractionation regime used was not seen. Dwarfism and exencephaly were the two most commonly observed malformations in all series.

Abnormalities, Radiation-Induced↗
PubMed1984

Transmission ratio distortion in mouse t-haplotypes is due to multiple distorter genes acting on a responder locus.

Transmission ratios of male mice heterozygous for various combinations of partial t-haplotypes provide evidence in support of a model for the genetic basis of ratio distortion, involving two or more distorter genes acting on a responder locus. The t form of the responder locus, Tcr, in the medial part of the haplotype, must be present and heterozygous for distortion to occur. When the responder alone is present, as in t low haplotypes, the chromosome carrying it is transmitted in a low ratio (less than 50%). The t forms of the distorter loci act additively, in cis or trans, to raise the transmission of whichever chromosome carries Tcr. Identified distorter loci are Tcd-1, in the proximal part of the haplotype, Tcd-2, distal to Tcr, and probably Tcd-3, lying between Tcr and Tcd-2. In the absence of Tcr the distorters are transmitted normally. The system is compared with the SD system of Drosophila.

Alleles↗
PubMed1984

Chromosome maps of man and mouse II.

Chromosome displays and listings are presented showing loci whose position is known in both man and mouse, in similar manner to our previous report (Dalton et al. 1981). There is now evidence for at least 27 conserved autosomal segments with two or more loci in the two species. The human and mouse chromosome maps show the location of homologous genes. The mouse map also shows the positions of translocations used in gene location and of some other genes used in linkage studies on them.

Animals↗
PubMed1984

Parental source of chromosome imprinting and its relevance for X chromosome inactivation.

In imprinting, homologous chromosomes behave differently during development according to their parental origin. Typically, paternally derived chromosomes are preferentially inactivated or eliminated. Examples of such phenomena include inactivation of the mammalian X chromosome, inactivation or elimination of one haploid chromosome set in male coccids, and elimination of paternal X chromosomes in the fly Sciara. It has generally been thought that the paternal chromosomes bear an imprint leading to their inactivation or elimination. However, alteration of the parental origin of chromosomes, as in the study of parthenogenotes in mammals and coccids, shows that passage of chromosomes through a male germ cell or fertilization is not essential for inactivation or elimination. It appears that neither chromosome set is programmed to resist or undergo inactivation. Instead the two sets differ in relative sensitivity, and the question is whether the maternal set have an imprint for resistance, or the paternal set one for susceptibility. Very early in development of mammals both X chromosomes are active. This makes it simpler to envisage the maternal X bearing an imprint for resistance to inactivation, which persists through the early developmental period. Similar considerations also apply in coccids and Sciara. Thus, imprinting should be regarded as a phenomenon conferred on the maternal chromosomes in the oocyte. This permits simpler models for the mechanism of X-inactivation, and weakens the case for evolution of X-inactivation from an earlier form of inactivation during male gametogenesis. One may speculate whether imprinting affects timing of gene action in development.

Animals↗
PubMed1984

Further studies on the effect of radiation during the storage of frozen 8-cell mouse embryos at -196 degrees C.

Frozen 8-cell mouse embryos were treated with radiation doses of 0, 10, 50, 100 or 200 cGy gamma-rays at a dose rate of congruent to 5 cGy/day. After thawing the embryos were scored for normal morphological appearance and for development to morulae and blastocysts after 24 h in culture. Embryos from each treatment were then separately transferred to the uteri of pseudopregnant foster mothers which were killed at Day 14 of pregnancy. There was no effect of radiation on morphological appearance, development to morulae and blastocysts, implantation rate, or on the ratio of live fetuses to the number of transferred embryos. As there appeared to be no detrimental effect of up to 200 cGy on frozen 8-cell mouse embryos and, as this is the equivalent of congruent to 2000 years of background radiation, it is concluded that normal levels of background radiation would not be a hazard to the long-term storage of mammalian embryos.

Animals↗