X-inactivation pattern in the epididymis of sex-reversed mice heterozygous for testicular feminization

Development ◽  
1974 ◽  
Vol 32 (1) ◽  
pp. 217-225
Author(s):  
Ulrich Drews ◽  
Valentin Alonso-Lozano
Keyword(s):  
X Chromosome ◽  
Sex Reversal ◽  
Cellular Level ◽  
X Inactivation ◽  
Testicular Feminization ◽  
Wild Type ◽  
Female Mice ◽  
Inactivation Pattern ◽  
Ultrastructural Appearance ◽  
Male Sex

Female mice heterozygous for testicular feminization were sex-reversed by means of the autosomal sex reversal mutation (Sxr). Due to X-inactivation, the blastemata for male sex organs in these animals are composed of a mixture of cells, carrying either the wildtype X chromosome or the X chromosome affected with Tfm in an active state. Thus, the two types of cells are sensitive to androgens or insensitive to androgens, respectively. This mosaic could be demonstrated in the epididymis on a cellular level. Segments of undifferentiated Tfm cells were found alternating with normally differentiated wild-type cells. The ultrastructural appearance of the mosaic is described.

X chromosome inactivation analysis reveals a difference in the biology of ET patients with JAK2 and CALR mutations

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2091-2093 ◽  
Author(s):  
Christopher Allen ◽  
Jonathan R. Lambert ◽  
David C. Linch ◽  
Rosemary E. Gale
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Wild Type ◽  
Key Points ◽  
Inactivation Pattern ◽  
Calr Mutations ◽  
Calr Mutation

Key Points In ET, a CALR mutation correlates with a monoclonal X chromosome inactivation pattern, which differs from JAK2V617F mutant disease. The presence of a CALR mutant is associated with suppression of wild-type myelopoiesis.

scholarly journals X chromosome choice occurs independently of asynchronous replication timing

2005 ◽  
Vol 168 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Joost Gribnau ◽  
Sandra Luikenhuis ◽  
Konrad Hochedlinger ◽  
Kim Monkhorst ◽  
Rudolf Jaenisch
Keyword(s):  
X Chromosome ◽  
Molecular Mechanisms ◽  
Replication Timing ◽  
S Phase ◽  
X Inactivation ◽  
Wild Type ◽  
Gene Deletions ◽  
Asynchronous Replication ◽  
Skewed X Inactivation

In mammals, dosage compensation is achieved by X chromosome inactivation in female cells. Xist is required and sufficient for X inactivation, and Xist gene deletions result in completely skewed X inactivation. In this work, we analyzed skewing of X inactivation in mice with an Xist deletion encompassing sequence 5 KB upstream of the promoter through exon 3. We found that this mutation results in primary nonrandom X inactivation in which the wild-type X chromosome is always chosen for inactivation. To understand the molecular mechanisms that affect choice, we analyzed the role of replication timing in X inactivation choice. We found that the two Xist alleles and all regions tested on the X chromosome replicate asynchronously before the start of X inactivation. However, analysis of replication timing in cell lines with skewed X inactivation showed no preference for one of the two Xist alleles to replicate early in S-phase before the onset of X inactivation, indicating that asynchronous replication timing does not play a role in skewing of X inactivation.

scholarly journals Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern

2021 ◽  
Vol 12 ◽  
Author(s):  
Luciane Simonetti ◽  
Lucas G. A. Ferreira ◽  
Angela Cristina Vidi ◽  
Janaina Sena de Souza ◽  
Ilda S. Kunii ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Intelligence Quotient ◽  
Klinefelter Syndrome ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Neurocognitive Dysfunction ◽  
Inactivation Pattern ◽  
Iq Scores

Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development (GTPBP6, EIF2S3, ITM2A, HUWE1, KDM5C, GDI1, and VAMP7) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than the four individuals who presented a skewed X-inactivation (SXI) pattern. The evaluation of gene expression showed higher GTPBP6 expression in KS patients with RXI than in controls (p = 0.0059). Interestingly, the expression of GTPBP6 in KS patients with SXI did not differ from that observed in controls. Therefore, our data suggest for the first time that GTPBP6 expression is negatively associated with full-scale IQ under the regulation of the type of XCI pattern. The SXI pattern may regulate GTPBP6 expression, thereby dampening the impairment in cognitive performance and playing a role in intelligence variability in individuals with KS, which warrants further mechanistic investigations.

scholarly journals Attempts to test the inactive-X theory of dosage compensation in mammals

1963 ◽  
Vol 4 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Mary F. Lyon
Keyword(s):  
X Chromosome ◽  
Adult Female ◽  
Dosage Compensation ◽  
Somatic Cells ◽  
Coat Colour ◽  
The Other ◽  
Wild Type ◽  
X Chromosomes ◽  
Female Mice ◽  
Colour Mutant

The inactive-X theory of dosage compensation postulates that in all somatic cells of adult female mammals one or other of the two X chromosomes is genetically inactive. This means that in a female heterozygous for two non-allelic genes acting through the same cells, and carried one on each X chromosome, one or other gene should act in all cells. Conversely, if the two genes are carried on the same X, then both genes should act in some cells and neither gene in the remainder. This point has been tested by breeding experiments with mice, using pairs of genes affecting coat colour and coat texture. In female mice carrying the colour mutant dappled, Modp, on one X and a translocation including the wild-type alleles of pink-eye, p, and albino, c, on the other, either Modp or the translocation acted in all cells. With the genes tabby, Ta and striated, Str, affecting coat texture, in Str + / + Ta females tabby acted only in the non-Str patches, while in StrTa/ + + it acted only in the Str ones. Thus these experiments confirm that only one of the two X chromosomes is active in the somatic cells of female mammals.

scholarly journals The pattern of X-chromosome inactivation in the embryonic and extra-embryonic tissues of post-implantation digynic triploid LT/Sv strain mouse embryos

1990 ◽  
Vol 56 (2-3) ◽  
pp. 107-114 ◽  
Author(s):  
S. Speirs ◽  
J. M. Cross ◽  
M. H. Kaufman
Keyword(s):  
X Chromosome ◽  
Sex Chromosome ◽  
Yolk Sac ◽  
X Inactivation ◽  
Tissue Samples ◽  
X Chromosomes ◽  
Embryonic Tissues ◽  
Inactive X Chromosome ◽  
Distinct Cell ◽  
Inactivation Pattern

SummarySpontaneously cycling LT/Sv strain female mice were mated to hemizygous Rb(X.2)2Ad males in order to facilitate the distinction of the paternal X chromosome, and the pregnant females were autopsied at about midday on the tenth day of gestation. Out of a total of 222 analysable embryos recovered, 165 (74·3%) were diploid and 57 (25·7%) were triploid. Of the triploids, 26 had an XXY and 31 an XXX sex chromosome constitution. Both embryonic and extra-embryonic tissue samples from the triploids were analysed cytogenetically by G-banding and by the Kanda technique to investigate their X-inactivation pattern. The yolk sac samples were separated enzymatically into their endodermally-derived and mesodermally-derived components, and these were similarly analysed, as were similar samples from a selection of control XmXp diploid embryos. In the case of the XmXmY digynic triploid embryos, a single darkly-staining Xm chromosome was observed in 485 (82·9%) out of 585, 304 (73·3%) out of 415, and 165 (44·7%) out of 369 metaphases from the embryonic, yolk sac mesodermally-derived and yolk sac endodermally-derived tissues, respectively. The absence of a darkly staining X-chromosome in the other metaphase spreads could either indicate that both X-chromosomes present were active, or that the Kanda technique had failed to differentially stain the inactive X-chromosome(s) present. In the case of the XmXmXp digynic triploid embryos, virtually all of the tissues analysed comprised two distinct cell lineages, namely those with two darkly-staining X-chromosomes, and those with a single darkly staining X-chromosome. Four X-inactivation patterns were consequently observed in this group, namely, (XmXp)Xm, (XmXm)Xp, (Xm)XmXp and XmXm(Xp) in which the inactive X is enclosed in parentheses. The incidence of these various classes varied among the tissues analysed. There was, however, a clear pattern of non-random selective paternal X-inactivation in yolk sac endodermally-derived samples which possessed two inactive X-chromosomes. This finding contrasts with the situation observed in the yolk sac mesodermally-derived and embryonic samples which possessed two inactive X-chromosomes, where the ratio of (XmXm)Xp:Xm(XmXp) was 1:1·20 and 1:1·03, respectively, being clear evidence that random X-inactivation had occurred in these tissues.

scholarly journals Age-related reactivation of an X-linked gene close to the inactivation centre in the mouse

1988 ◽  
Vol 52 (2) ◽  
pp. 151-154 ◽  
Author(s):  
Sheila Brown ◽  
Sohaila Rastan
Keyword(s):  
X Chromosome ◽  
Reciprocal Translocation ◽  
Coat Colour ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Wild Type ◽  
Linked Gene ◽  
Female Mice ◽  
Age Related ◽  
Type Gene

SummaryAge-related reactivation of an X-linked gene which maps close to Xce, the X chromosome inactivation centre, has been observed. In five female mice which carried the X-linked coat colour gene Moblo on the reciprocal translocation T(X;16)16H (Searle's translocation), and the wild-type gene on the normal X chromosome, and therefore expressed the Moblo phenotype due to the non-random inactivation characteristic of Searle's translocation, progressive darkening of the coat was observed as the animals aged. This is due to reactivation of the previously inactivated wild-type gene at the Mo locus on the normal X chromosome. As the Mo locus is located 4 cM distal to Xce, the X chromosome inactivation centre, these observations provide evidence of age-related instability of inactivation of an X-linked gene close to the inactivation centre.

Unbalanced X;Autosome Translocations May Lead to Mild Phenotypes and Are Associated with Autoimmune Diseases

2020 ◽  
Vol 160 (2) ◽  
pp. 80-84
Author(s):  
Claudia Ciaccio ◽  
Serena Redaelli ◽  
Angela Bentivegna ◽  
Susan Marelli ◽  
Francesca Crosti ◽  
...  
Keyword(s):  
X Chromosome ◽  
Clinical Presentation ◽  
Autoimmune Disorders ◽  
X Inactivation ◽  
Compensation Mechanism ◽  
Inactivation Pattern ◽  
Family Testing ◽  
Wide Variability ◽  
Mild Clinical Presentation ◽  
Skewed X Chromosome Inactivation

Unbalanced X;autosome translocations are a rare occurrence with a wide variability in clinical presentation in which the X chromosome unbalance is usually mitigated by a favorable X inactivation pattern. In most cases, this compensation mechanism is incomplete, and the patients show a syndromic clinical presentation. We report the case of a family with 4 women, of 3 different generations, carrying an unbalanced X;7 translocation with a derivative X;7 chromosome and showing a skewed X inactivation pattern with a preferential activation of the normal X. None of the carriers show intellectual disability, and all of them have a very mild clinical presentation mainly characterized by gynecological/hormonal issues and autoimmune disorders. We underline the necessity of family testing for a correct genetic consultation, especially in the field of prenatal diagnosis. We indeed discuss the fact that X;autosome translocations may lead to self-immunization, as skewed X chromosome inactivation has already been proved to be related to autoimmune disorders.

scholarly journals The differential staining pattern of the X chromosome in the embryonic and extraembryonic tissues of postimplantation homozygous tetraploid mouse embryos

1992 ◽  
Vol 59 (3) ◽  
pp. 205-214 ◽  
Author(s):  
S. Webb ◽  
T. J. de Vries ◽  
M. H. Kaufman
Keyword(s):  
X Chromosome ◽  
High Efficiency ◽  
Indirect Evidence ◽  
X Inactivation ◽  
Differential Staining ◽  
Hybrid Female ◽  
Cell Stage ◽  
X Chromosomes ◽  
F1 Hybrid ◽  
Inactivation Pattern

Summary(C57BL × CBA)F1 hybrid female mice were mated with hemizygous Rb(X.2)2Ad males to distinguish the paternal X chromosome. Homozygous tetraploids were produced by blastomere fusion at the 2-cell stage, and 161 of these were transferred to recipients and analysed on the 10th day of gestation. 59 implants contained resorptions and 76 contained either an embryo and/or extraembryonic membranes. 38 (20, XXXX and 18, XXYY) were analysed to investigate their X-inactivation pattern. Embryonic and yolk sac endodermally- and mesodermally-derived samples were analysed by G-banding and by Kanda analysis. In the XX and XY controls, the predicted pattern of X-inactivation was observed, though 12·2% of metaphases in the XX series displayed no X-inactivation. In the XY series the Y chromosome was seen in a high proportion of metaphases.In the XXXX tetraploids, 8 cell lineages were recognized with regard to their X-inactivation pattern, though most belonged to the following 3 categories: (XmXm)XpXp, Xm(XmXp)Xp and XmXm(XpXp). The other categories were only rarely encountered. In the embryonic and mesodermally-derived tissue the ratio of these groups was close to 1:2:1, whereas in the endodermally-derived tissue it was 1:4·11:4·88, due to preferential paternal X-inactivation. A significant but small proportion of all 3 tissues analysed displayed no evidence of X-inactivation. Indirect evidence suggests that this represents a genuine group because of the high efficiency of the Kanda staining. The presence of the Xm(XmXp)Xp category is consistent with the expectation that X-inactivation occurs randomly in 2 of the 4 X chromosomes present. The presence of small numbers of preparations with no evidence of X-inactivation and other unexpected categories suggests that these are probably selected against during development.

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