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C V Beechey

Publications and source records attributed to C V Beechey.

At least 55 records · Page 3Linked to original sources
PubMed1983

Two new X-autosome translocations in the mouse.

The reciprocal translocations T(X;4)37H and T(X;11)38H were induced by acute X-irradiation of spermatozoa. Male heterozygotes are completely aspermic with a spermatogenic block at pachytene and testis masses about one third of normal, though metaphase I is very occasionally reached in T37H. For both translocations the X chromosome breakpoints are in band XA2, and the autosomal breakpoints are in 4D3 for T37H and 11E1 for T38H, leading to long and short marker chromosomes. Chain quadrivalents predominated in oocytes at MI, with no rings; there were 32% trivalent + univalent configurations in T37H and 40% in T38H. These generated (1) XO mice, (2) tertiary trisomics carrying 20 bivalents and the small X4 (T37H) or X11 (T38H) markers. These trisomics were apparently lethal in T37H but sub-viable in T38H and sometimes fertile as XX11 and trisomic XXX11 females, though sterile as XX11Y males. However, many developed exencephaly in utero, probably because of the distal duplication on chromosome 11. No tertiary monosomics were found in 12 to 14 day embryos. Seven percent of all female progeny were XO, with a higher than expected frequency in T37H and a lower than expected one in T38H. T37H is about two units and T38H about five units from the spf locus on the X chromosome with evidence for some crossover suppression between the T38H breakpoint and Ta. Autosomal linkages found were T37H-m-b (R.F. of 16 +/- 4% between T37H and m) and T38H-Rewc (R.F. of 5 +/- 3%). T37H/+ females weighed about 10% less than normal females at birth and about 30% less at weaning; there was little if any effect in T38H/+ females or in males carrying either translocation. Neither translocation had any marked effect on viability. T37H/+ females showed variegation when heterozygous for b with the wild type allele in the long 4X marker. On average, about 20% of the coat was brown rather than black. However, no clear evidence for m variegation was found.

Animals↗
PubMed1983

A male-sterile insertion in the mouse.

Is(7;1)40H was found in the daughter of a male mouse given spermatozoal X-irradiation. It is a non-inverted insertion of about half of chromosome 7 into chromosome 1, generating a long somatic marker chromosome. Breakpoints are in bands 1B, 7B1, and 7F1; linkage tests show that these breakpoints are about midway between fz and In on the 1, and 0.2 units distal to ru-2 and 12 units proximal to fr on the 7. Female carriers had litters of about one-third normal size and showed some decline in length of reproductive life. Males were sterile, with testis weights only 30% of normal and with abrupt cessation of spermatogenesis in pachytene at stage IV of the seminiferous epithelial cycle. Positive sex-vesicle contact with the insertional configuration was found in only 40% of pachytene spermatocytes, which suggested that other factors may be involved in the spermatogonial breakdown. In oocytes at metaphase I 76% of insertion configurations were multivalent, because of one or more chiasmata in the inserted segment, as were 79% of synaptonemal complex configurations in male pachytenes. Karyotyping at 12.5 to 14.5 days of gestation showed that all embryos with duplications of the inserted segment were exencephalic, and the only example of a corresponding deficiency was retarded. Analysis of the consequences of heterozygosity for the insertion shows that the insertion length should be correlated with the frequency of unbalanced offspring and thus with the amount of F1 lethality. The genetic length of 36 cM estimated in this way from data on liveborn offspring is in reasonable agreement with estimates from cytological measurements and meiotic configurations but rather higher than that from linkage tests.

Animals↗
PubMed1982

Cytogenetic effects of protracted gamma exposures from conception of male mice.

In order to gain an overall picture of the genetic effects of an increased level of background radiation it is necessary to study the results of protracted exposures to embryonic and immature germ-cell stages as well as to stages found in the mature organism. For this purpose, litters produced by female mice, kept in a 10 or 20 rad/day 60 Co gamma-irradiation field, were kept in the same fields from conception until about 60 days later, having absorbed doses of 526 and 1078 rad respectively. Tests on exposed female offspring showed them to be sterile. 8 weeks after removal from the gamma field, mean testis masses of males in the 20 rad/day series were only half normal but those receiving 10 rad/day were little affected. Frequencies of translocations in spermatocytes at diakinesis/metaphase I were only slightly increased in the exposed series, differences not being significant. Estimated rates of translocation induction were around 5 x 10(-6) per rad, about one-third of those found after protracted gamma-irradiation of stem-cell spermatogonia in the adult. Embryonic lethality in progeny of other similarly irradiated males(absorbed doses of 560 and 1040 rad), mated 2 months after removal from the radiation fields, was also increased slightly, but not significantly. Results are compared with others on the induction of chromosome aberrations and gene mutations, mainly by acute irradiation, in prenatal and neonatal male mice. It is concluded that early male germ-cell stages generally show a reduced genetic radiosensitivity after both acute and chronic exposures.

Animals↗
PubMed1982

Dominant lethal and ovarian effects of plutonium-239 in female mice.

In two separate experiments (C3H x 101)F1 female mice were injected intravenously with 239Pu in trisodium citrate, then mated in pairs to strain CBA males, to test for dominant lethality. In the first experiment 10 muCi kg-1 and in the second 20 muCi kg-1 body mass was injected. Matings were after 6 days in the first experiment (estimated ovarian absorbed dose of 0.1 Gy) and after 3, 6 or 12 weeks in the second (estimated ovarian doses of 1.11, 2.45 and 5.91 Gy respectively). No evidence of dominant lethal induction was found in the first experiment, but in the second there was a significant increase over controls in pre-implantation loss in all three series. Post-implantation lethality increased significantly (by 12 per cent) only after 12 weeks' exposure. With the 6- and 12-week exposures (especially the latter) luteal counts fell and fewer females became pregnant than in controls. This is attributed to oocyte killing by the alpha-particles. Histological and autoradiographic investigations showed a marked reduction in ovarian size and follicular numbers with fission-tracks clustered mainly over the medullary stroma. The pre-implantation loss may stem from lowered fertilization of oocytes because of their damage, so that the best measure of dominant lethality is that based on post-implantation death. Thus there is only slight evidence for the induction of genetic damage, which is in line with previous findings after chronic exposures of female mice.

Animals↗
PubMed1982

The use of Robertsonian translocations in the mouse for studies on non-disjunction.

In the mouse, gametes with gross chromosome duplications and deficiencies can complement each other to give viable zygotes (with some notable exceptions involving particular chromosomes). These complementation-type offspring can be recognised in intercrosses between translocation heterozygotes in which one parent is homozygous for a recessive genetic marker not carried by the other. This system has beeN used by Lyon and colleagues (1976) to study non-disjunction in heterozygotes for tobacco mouse and laboratory-derived Robertsonian translocations. Although non-disjunction is frequent in the former group, still higher frequencies are needed for a workable test system in which wild type mice are treated and mated to a tester stock generating many aneuploid gametes. Possible approaches include (1) use of semidominant markers, (2) marking both arms, (3) combining two or three independent Robertsonians in the tester stock, (4) use of compounds of Robertsonians wih monobrachial homology, since these give very high frequencies of non-disjunction, (5) generation of a compound of three Robertsonians with tribrachial homology, which should produce aneuploid gametes only. This last seems the most promising approach, if the compound proves fertile, and would be analogous to the isochromosome system of Drosophila.

Aneuploidy↗
PubMed1981

The effects of radiation dose-rate and quality on the induction of dominant lethals in mouse spermatids.

Hybrid male mice were given 3 Gy (300 rad) doses of X- or gamma-irradiation at dose-rates of either 0.6 or 0.002 Gy/min for each radiation. Germ-cells treated as spermatids were tested for dominant lethality. Effects on spermatogonia were evaluated by studying testis-weight, sperm-count and sperm abnormalities. The rate of induction of dominant lethal mutations was 2.1 times as high after acute X-irradiation as after protracted gamma-irradiation. Most of this difference resulted from the change in radiation quality, since the relative effectiveness of X- versus gamma-irradiation was 1.9 at low and 1.6 at high dose rates. For each radiation, however, fewer dominant lethals were induced at low dose-rates than at high (low/high ratios of 0.8 and 0.9 respectively) although differences did not reach a significant level. There were no statistically significant effects of dose rate on testis-weight or sperm-count in the X-ray series, but there were significantly less severe effects on both with protraction of the gamma-irradiation. Evidence for effects of radiation quality on these characters was conflicting. Frequencies of abnormal spermatozoa were markedly increased 7 weeks after irradiation but there were no consistent effects of radiation intensity or quality.

Animals↗
PubMed1980

Linkage analyses of murine immunoglobulin heavy chain and serum prealbumin genes establish their location on chromosome 12 proximal to the T (5;12) 31H breakpoint in band 12F1.

Analysis of backcross mice carrying the Harwell translocation T(5;12)31H has led to the definitive localization of the immunoglobulin heavy chain gene cluster. Both Igh-1 and Pre-1 loci were found to segregate in tight linkage with the chromosomal markers 5(12) and 12(5), which define the balanced translocation T(5;12)31H. Additional data establish the location of these genes at the telomeric end of chromosome 12. That both loci are proximal to the chromosomal breakpoint in band 12F1 is shown by the phenotypes of segregants aneuploid for the presence or absence of the small marker 5(12). The order of loci inferred from a single recovered recombinant is: centromere-Igh-1-Pre-1-T(5;12)31H.

Animals↗
PubMed1980

Comparative effects of protracted exposures to 60Co gamma-radiation and 239Pu alpha-radiation on breeding performance in female mice..

Breeding performances are compared of hybrid female mice given 239Pu (5 or 10 mu Cikg-1 body mass in 1% trisodium citrate via the tail-vein), or kept in a 10 rad/day or 20 rad/day 60Co gamma-irradiation field (but mated in the control area), or unirradiated. Ovarian dose-rates from the injected plutonium were initially 0.8 and 1.7 rad/day, changing little thereafter; actual gamma-ray dose-rates to breeding females averaged around 8 and 16 rad/day respectively. Both gamma-ray treatments affected reproductive performance more than the plutonium injections, with respet to duration of fertility and to offspring per litter in successive 4-weekly periods, though overall mean litter-sizes were not significantly less than controls. The r.b.e. for these effects on reproduction, attributed to germ-cell killing, is about 2.5 for the alpha-particles vs. gamma-rays, lower than for testis mass reduction in males. This low r.b.e. may be connected with inhomogeneity of alpha-particle dose within the ovary, but it is known that fission neutron versus gamma r.b.e.'s for impairment of female fertility are also lower than those for impairment of male fertility.

Alpha Particles↗
PubMed1979

A disruption of pachytene DNA metabolism in male mice with chromosomally-derived sterility.

DNA metabolism was analyzed in spermatocytes of mice that were sterile either because of X-autosome or autosome-autosome translocations, or because of trisomy. In the strains analyzed, spermatogenic development is arrested by metaphase I or soon thereafter. In all such strains a disruption of the normal pattern of pachytene DNA metabolism occurred. Prepachytene metabolism appeared normal. Disruption was manifest in both the level of endogenously generated nicks during pachytene and in the distribution of nicks among the different DNA sequence classes. Nicking was more intense in the steriles and tended to be randomized in distribution. Satellite DNA underwent pachytene nick-repair in the steriles but not in fertile controls. The repair capacity of spermatocytes from steriles was equal to that of the fertiles; the higher frequency of nicks in the steriles was due to a persistence of nicking activity.

Animals↗
PubMed1979

Colinearity in the mouse genome: a study of chromosome 2.

The cytologic positions (determined by G-banding) of the breakpoints on mouse chromosome 2 of a series of ten reciprocal translocations were compared with their most probable genetic positions on the linkage map, as determined by studies on recombination with known chromosome 2 (= linkage group V) markers. The most probable proximaldistal orders of the genetic and cytologic breakpoints were found to be the same; i.e., the two sets of breakpoints were colinear. However, there was no close correspondence between these two measures of the distance apart of adjacent breakpoints, since some translocation breaks which were well separated in G-band positions seemed close together in terms of the linkage map, and vice versa. This helps to confirm LYON'S conclusion that in certain mouse chromosomes, including No. 2, the distribution of chiasmata is nonrandom.

Animals↗
PubMed1976

Cytogenetic effects of protracted exposures to alpha-particles from plutonium-239 and to gamma-rays from cobalt-60 compared in male mice.

Adult C3H X 101 hybrid male mice were injected intravenously with 4 muCi of 239Pu citrate per kg body weight and examined for evidence of cytogenetic damage to the testis after exposures of 21, 28 and 34 weeks, with average doses from alpha-particles estimated as 13, 18 and 18 rad respectively (mean dose rate 0.00006 rad/min). Results were compared with those obtained when equivalent males were exposed continuously and concurrently to 1128 rad 60Co gamma-irradiation over 28 weeks (0.004 rad/min). The following estimates of the relative effectiveness of the alpha- and gamma-radiation were made: 24 for reciprocal translocations and for chromosome fragments, 22 for dominant lethal mutations acting after implantation. These values (with mean of 23) are based on average testis doses, with no correction for probable non-homogeneity of alpha dose distribution. In the mice exposed to gamma-irradiation there were significant reductions in testis mass and epididymal sperm-count. Although corresponding differences from control were not significant in the alpha series, consideration of results from a previous experiment by the same authors [2] allowed the relative effectiveness of the alpha- and gamma-irradiation for testis mass reduction to be estimated as roughly 10-15. Existing data on translocation induction in mouse spermatogonia by low dose-rates of gamma-rays (down to 0.003 rad/min) were analysed. They suggested that minimum rates of induction at very low intensities were not less than 1 X 10(-5) translocations per rad. A comparison of the frequencies of induction of fragments and of sperm-head abnormalities obtained after chronic gamma-ray exposures in the present experiment with those found by other workers after acute X-ray exposures suggested that there were no marked dose-rate effects with these types of mutational effect. Finally, the special problems associated with cytogenetic studies on alpha-emitters are discussed.

Alpha Particles↗