Analysis of Gynandromorph Survivals in DROSOPHILA MELANOGASTER Infected with the Male-Killing Sr Organisms

The effects of SRO (Sex-ratio organism; previously called SR spirochetes) infection on the viability of gynandromorphs of D. melanogaster were examined. A fraction of gynadromorphs, most of them with small areas of XO tissue, survived, but the majority were not viable when XO nuclei or cells are affected by the infecting SRO. Apparently the replacement of lethal XO nuclei or cells by adjacent XX ones does not take place. Some possibilities are discussed as to the time and the primary site of the lethal action of SRO.     

Relative DNA content in lymphocytes and buccal mucosa of patients with sex chromosomal anomalies

Cytophotometric estimation of DNA values from human buccal mucosa and lymphocyte culture nuclei shows a difference related to different X chromosomal abnormalities, namely, del X, XO, XXX and XXY. The values in the buccal mucosa in all cases except XXX were similar to the normal XX and XY. In lymphocytes nuclei, however, a steady increase in the DNA content at a significant level could be related to an increase in the number of X chromosomes. The similarity in the DNA values of normal XX and XY controls may be attributed to asynchrony in the replication patterns of X and Y chromosomes.     

Two maternally derived X chromosomes contribute to parthenogenetic inviability

In certain extraembryonic tissues of normal female mouse conceptuses, X-chromosome-dosage compensation is achieved by preferential inactivation of the paternally derived X. Diploid parthenogenones have two maternally derived X chromosomes, hence this mechanism cannot operate. To examine whether this contributes to the inviability of parthenogenones, XO and XX parthenogenetic eggs were constructed by pronuclear transplantation and their development assessed after transfer to pseudopregnant recipients. In one series of experiments, the frequency of postimplantation development of XO parthenogenones was much higher than that of their XX counterparts. This result is consistent with the possibility that two maternally derived X chromosomes can contribute to parthenogenetic inviability at or very soon after implantation. However, both XO and XX parthenogenones showed similar developmental abnormalities at the postimplantation stage, demonstrating that parthenogenetic inviability is ultimately determined by the possession of two sets of maternally derived autosomes.     

Developmental retardation of XO mouse embryos at mid-gestation.

It is not known why XO mouse embryos, which develop more slowly than XX embryos until early mid-gestation, reach the same stage in their growth and development as their XX littermates at the mid-gestation stage. It is hypothesized that there is an effect of 'litter size' that causes an acceleration of the development of XO embryos at mid-gestation. The present study was performed to determine whether the development of XO embryos is retarded compared with that of their XX litermates at early mid-gestation (day 8 of gestation), before reduction of litter size. The percentage of pre-somite stage XO embryos was greater than the percentage of pre-somite stage XX embryos, and the mean number of somites was greater in XX embryos than it was in XO embryos. These findings indicate that the development of XO embryos was retarded when compared with that of their XX litermates at early mid-gestation. This result is discussed with respect to the compensatory development of XO embryos at mid-gestation and the reduction of litter size shortly after early mid-gestation.     

Teratogen susceptibility of XO mothers and XO embryos in mice

We examined whether the chromosomal imbalance inherent in an XO constitution in mice is more susceptible to teratogenic influence of biotin deficiency using a newly established mouse colony with pure X monosomy. We hypothesized that XO mothers or XO embryos might be more susceptible to certain teratogens. Contrary to our expectation, the incidence of external malformations induced by biotin deficiency did not differ either between XX dams and XO dams or between XX fetuses and XO fetuses.     

Some characteristics of the XO mouse (Mus musculus L.) I. Vitality: Growth and metabolism

The growth rate of XO mice during the first five weeks of life was shown to be significantly lower (ca. 15%) than the growth rate of normal XX mice. A marker gene Tabby was introduced in order to recognize hemizygous XO females. The presence or absence of this gene had a significant influence on growth rates. XO females could only be compared to XX females in an indirect way. The differences found could not be attributed to maternal influence or to the influence of litter size.Body temperature and thyroid activity were found to be lower in XO mice than in normal females. It is suggested that the lower growth rate characteristic of the XO mice is a consequence of hypothyroidism and a lower basal metabolic rate.The results show that phenotypically XO mice are not entirely normal and at least two normal X's are necessary for complete development.     

棕色田鼠XO雌体育性研究

通过对棕色田鼠外形特征,卵巢切片,怀胎和生产雌鼠染色体鉴定等方面研究,证实了该鼠ＸＯ雌鼠可孕,并具有生殖能力。染色体鉴定表明,ＸＸ雌体中的两条Ｘ性染以体,一条为Ｍ类型另一条为ＳＭ类型;ＸＯ雌体中的Ｘ性染色体为Ｍ类型。所以ＸＯ雌性的生育能力可能与Ｘ染色体有关,其上可能存在雌性育性基因。     

Extragenic suppressors of a dominant masculinizing her-1 mutation in C. elegans identify two new genes that affect sex determination in different ways

Summary: The her-1 regulatory switch gene in C. elegans sex determination is normally active in XO animals, resulting in male development, and inactive in XX animals, allowing hermaphrodite development. The her-1(n695gf) mutation results in the incomplete transformation of XX animals into phenotypic males. We describe four extragenic mutations that suppress the masculinized phenotype of her-1(n695gf) XX. They define two previously undescribed genes, sup-26 and sup-27. All four mutations exhibit semidominance of suppression and by themselves have no visible effects on sex determination in otherwise genotypically wild-type XX or XO animals. Analysis of interactions with mutations in the major sex-determining genes show that sup-26 and sup-27 influence sex determination in fundamentally different ways. sup-26 appears to act independently of her-1 to negatively modulate synthesis or function of tra-2 in both XX and XO animals. sup-27 may play a role in X-chromosome dosage compensation and influence sex determination indirectly.     

H-Y antigen in Turner's syndrome patients with different sex chromosome constitutions

Summary H-Y antigen was determined in seven XO-, nine XO/XX patients, in one patient with i(Xq), and in one patient with a mosaic XO/XYqh-. It turned out that all patients are H-Y antigen positive, confirming the results of earlier investigations of H-Y antigen in patients with Turner's syndrome. The results in XO/XX mosaics clearly demonstrate that the XO-cell is H-Y antigen positive and support the view of a regulatory gene for H-Y antigen gene expression which is located on the X chromosome.     

Activity of the Sex-Determining Gene tra-2 Is Modulated to Allow Spermatogenesis in the C. ELEGANS Hermaphrodite

In the nematode C. elegans, there are two sexes, the self-fertilizing hermaphrodite (XX) and the male (XO). The hermaphrodite is essentially a female that makes sperm for a brief period before oogenesis. Sex determination in C. elegans is controlled by a pathway of autosomal regulatory genes, the state of which is determined by the X:A ratio. One of these genes, tra-2, is required for hermaphrodite development, but not for male development, because null mutations in tra-2 masculinize XX animals but have no effect on XO males. Dominant, gain-of-function tra-2 mutations have now been isolated that completely feminize the germline of XX animals so that they make only oocytes and no sperm and, thus, are female. Most of the tra-2(dom) mutations do not correspondingly feminize XO animals, so they do not appear to interfere with control by her-1, a gene thought to negatively regulate tra-2 in XO animals. Thus, these mutations appear to cause gain of tra-2 function in the XX animal only. Dosage studies indicate that 5 of 7 tra-2(dom) alleles are hypomorphic, so they do not simply elevate XX tra-2 activity overall. These properties suggest that in the wild type, tra-2 activity is under two types of control: (1) in males, it is inactivated by her-1 to allow male development to occur, and (2) in hermaphrodites, tra-2 is active but transiently inactivated by another, unknown, regulator to allow hermaphrodite spermatogenesis; this mode of regulation is hindered by the tra-2(dom) mutations, thereby resulting in XX females.     

Somatic damage to the X chromosome of the nematode Caenorhabditis elegans induced by gamma radiation

Summary Wild-type male embryos and young larvae of the nematode Caenorhabditis elegans were more sensitive than wild-type hermaphrodites to inactivation by gamma rays; wild-type males have one X chromosome per cell (XO), whereas wild-type hermaphrodites have two (XX). Furthermore, after transformation into fertile hermaphrodites by a her-1 mutation, XO animals were more radiosensitive than XX her-1 animals; and XX animals transformed into fertile males by a tra-1 mutation did not show increased radiosensitivity. It is concluded that wild-type males are more radiosensitive than wild-type hermaphrodites because they have one X chromosome rather than two, and the predominant mode of inactivation of XO animals involves damage to the single X chromosome. No sex-specific differences in survival were observed after UV irradiation.     

X chromosome expression during oogenesis in the mouse.

The activities of glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) have been assayed in mouse oocytes at several stages of follicle development isolated from XX and XO female mice. Throughout the entire growth period the activity of G6PD was proportional to the number of X chromosomes present in the oocyte, whereas no difference in LDH activity was detected between XX and XO oocytes. It is concluded, therefore, that both X chromosomes are functional throughout oogenesis.     

Perinatal oocyte loss in XO mice and its implications for the aetiology of gonadal dysgenesis in XO women

Postnatally, XO mice have approximately half as many oocytes as their XX sisters. A quantitative histological analysis of XO and XX ovaries throughout oogenesis (14 1/2-24 1/2 days post coitum) revealed that this oocyte deficiency in XO mice is due to excess atresia of oocytes at the late pachytene stage (19 1/2 days post coitum). Female mice heterozygous for a large X inversion (In(X)/X mice) were also found to have excess atresia at late pachytene. It was suggested that in XO mice it is the presence of an unpaired X chromosome, and in In(X)/X mice, the incompleteness of X chromosome pairing, which leads to this excess oocyte atresia. A new quantitative histological procedure which was developed for the analysis of perinatal mouse ovaries is also described.     

Evidence that postnatal growth retardation in XO mice is due to haploinsufficiency for a non-PAR X gene

XO Turner women, irrespective of the parental source of the X chromosome, are of short stature, and this is now thought to be largely a consequence of haploinsufficiency for the pseudoautosomal region (PAR) gene SHOX. X(p)O mice (with a paternal X) are developmentally retarded in fetal life, are underweight at birth, and show reduced weight gain in the first few weeks after birth. X(m)O mice, on the other hand, are more developmentally advanced than their XX siblings in fetal life; their postnatal growth has not hitherto been assessed. Here we show that X(m)O mice are not underweight at birth, but they nevertheless show reduced weight gain postnatally. The fact that postnatal growth is affected in X(p)O and X(m)O mice, means that this must be due to X dosage deficiency. In order to see if haploinsufficiency for a PAR gene was responsible for this growth deficit (cf SHOX deficiency in Turner women), X(m)Y*(X) females, in which the Y*(X) chromosome provides a second copy of the PAR, were compared with XX females. These X(m)Y*(X) females were also growth-retarded relative to their XX sibs, suggesting that it may be haploinsufficiency for a non-dosage-compensated X gene or genes outside the PAR that is responsible for the postnatal growth deficit in XO mice. The X genes known to escape X inactivation in the mouse have closely similar Y homologues. X(m)YSRY-negative females were therefore compared with XX females to see if the presence of the SRY-negative Y chromosome corrected the growth deficit; this proved to be the case. The postnatal growth deficit of XO mice is therefore probably due to haploinsufficiency for a non-dosage-compensated X gene that has a Y homologue that provides an equivalent function in the somatic tissues of males.     

Chromosomal Abnormalities and Their Relation to Disease

When human chromosome anomalies were first described in 1959, it appeared that specific abnormalities might be correlated with specific syndromes. Mongolism and the D and E syndromes are examples of specific syndromes associated with the presence of an extra autosome. Klinefelter''s syndrome may be associated with a variety of different sex chromosome anomalies including XXY, XXYY, XXXY and XXXXY. The lastnamed variant is the only one that frequently presents features distinguishing it from the others. An XO sex chromosome complex is found in many women with gonadal dysgenesis. However, a variety of mosaicisms have been described in association with this condition, including XO/XX, XO/XXX, XO/XX/XXX, XO/XY and XO/XYY. Extra X chromosomes in phenotypical females do not seem to impair fertility or be consistently associated with congenital anomalies. Two families are described in which chromosome anomalies were found, but the association with defects was irregular. In one family the abnormality involved one of the number 16 chromosomes and in the other it involved one of the small acrocentric chromosomes.