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The management of the DNA double-strand breaks (DSBs) in the [G.sub.2] phase of the mitotic cycle of any DNA-bearing organism, especially mammals is explained. The study shows that a process called homologous recombinational pair (HRR) is used widely for repairing the DSBs.

The effects of X-linked imprinting on neurodevelopment, brain function and behavior are discussed. Sex-specific gene expression are responsible for inducing the development of sexually dimorphic features and for attenuating sex differences elicited as a result of differential hormone levels in males and females.

The mouse Y chromosome carries 10 distinct genes or gene families that have open reading frames suggestive of retained functionality; it has been assumed that many of these function in spermatogenesis. However, we have recently shown that only two Y genes, the testis determinant Sry and the translation initiation factor Eif2s3y, are essential for spermatogenesis to proceed to the round spermatid stage. Thus, any further substantive mouse Y-gene functions in spermatogenesis are likely to be during sperm differentiation. The complex Ssty gene family present on the mouse Y long arm (Yq) has been implicated in sperm development, with partial Yq deletions that reduce Ssty expression resulting in impaired fertilization efficiency. Here we report the identification of a more extensive Yq deletion that abolishes Ssty expression and results in severe sperm defects and sterility. This result establishes that genetic information (Ssty?) essential for normal sperm differentiation and function is present on mouse Yq.

The meiotic properties of paracentric inversion heterozygotes have been well studied in insects and plants, but not in mammalian species. In essence, a single meiotic recombination event within the inverted region results in the formation of a dicentric chromatid, which usually breaks or is stretched between the two daughter nuclei during the first meiotic anaphase. Here, we provide evidence that this is not the predominant mode of exchange resolution in female mice. In sharp contrast to previous observations in other organisms, we find that attempts to segregate the dicentric chromatid frequently result not in breakage, stretching, or loss, but instead in precocious separation of the sister centromeres of at least one homolog. This often further results in intact segregation of the dicentric into one of the meiotic products, where it can persist into the first few embryonic divisions. These novel observations point to an unusual mechanism for the processing of dicentric chromosomes in mammalian oogenesis. Furthermore, this mechanism is rare or nonexistent in mammalian spermatogenesis. Thus, our results provide additional evidence of sexual dimorphism in mammalian meiotic chromosome behavior; in 'stressful' situations, meiotic sister chromatid cohesion is apparently handled differently in males than in females.

It has previously been shown that abnormal placental development, i.e., hyper- and hypoplasia, occurs in crosses and backcrosses between different mouse (Mus) species. These defects are caused mainly by abnormal growth of the spongiotrophoblast. The precise genetic basis for these placental malformations has not been determined. However, a locus that contributes to the abnormal development (Ihpd: interspecific hybrid placental dysplasia) has been mapped to the X chromosome. The X-chromosomal location of Ihpd and its site of action, that is the spongiotrophoblast, mean that normally only the maternally inherited Ihpd locus is active even in female fetuses. However, by making use of the X-chromosomal inversion In(X)1H, we have produced interspecific hybrid [X.sup.p]0, in which the active X chromosome was inherited from Mus macedonicus males. In contrast to XX female and XY male conceptuses from this cross, which have hypoplastic placentas, the [X.sup.p]0 female conceptuses have hyperplastic placentas. This finding supports the view that it is expression of the M. macedonicus Ihpd locus in the spongiotrophoblast that leads to hyperplasia due to an abnormal interaction with M. musculus autosomal loci.

Ube1y is a Y-linked gene transcribed in the testis, which maps to a region of the mouse Y required for normal spermatogonial proliferation. Ube1y, together with a ubiquitously expressed homologue on the X chromosome (Ube1x), encodes ubiquitin-activating enzyme E1, an enzyme essential for eukaryotic cell proliferation. Ube1y is thus a strong candidate for the Y function in spermatogonial proliferation. Using probes specific for the two genes, we have used Northern analysis and RNase protection to assess transcript levels throughout testis development and, by using germ cell-deficient XXSx[r.sup.a] testes and purified cell fractions, we have defined the testicular cell types in which transcription occurs. Ube1y transcripts are already detectable in the fetal testis at 12.5 dpc, with higher levels at 14.5 dpc and then falling to low levels by the time of birth. Postnatally levels rise sharply, peaking at 10 dpp. Analysis of XXSx[r.sup.a] testes indicates that the bulk of the Ube1y transcription is in germ cells. The analysis of purified cell fractions shows that X- and Y-encoded transcripts are present in A spermatogonia, both are at very low levels (or perhaps absent) in pachytene spermatocytes and then return to high levels in round spermatids. The reactivation of transcription in round spermatids implies a requirement for the ubiquitination pathway at this time. The presence of Ube1x transcripts in A spermatogonia raises the question as to why Ube1y transcripts are required. This question is discussed in relation to the spermatogenic failure in XSx[r.sup.b]O mice which are deleted for Ube1y and it is argued that Ube1y serves to increase UBE1 production at a time of high demand. Ube1y transcripts were also detected in XXY and XY ovaries.

Abstract Background X monosomic mice (39,XO) have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO). The generally accepted hypothesis to explain this discrepancy is that the number of genes on the mouse X chromosome which escape X inactivation, and thus are expressed at higher levels in females, is very small. However this hypothesis has never been tested and only a small number of genes have been assayed for their X-inactivation status in the mouse. We performed a global expression analysis in four somatic tissues (brain, liver, kidney and muscle) of adult 40,XX and 39,XO mice using the Illumina Mouse WG-6 v1_1 Expression BeadChip and an extensive validation by quantitative real time PCR, in order to identify which genes are expressed from both X chromosomes. Results We identified several genes on the X chromosome which are overexpressed in XX females, including those previously reported as escaping X inactivation, as well as new candidates. However, the results obtained by microarray and qPCR were not fully concordant, illustrating the difficulty in ascertaining modest fold changes, such as those expected for genes escaping X inactivation. Remarkably, considerable variation was observed between tissues, suggesting that inactivation patterns may be tissue-dependent. Our analysis also exposed several autosomal genes involved in mitochondrial metabolism and in protein translation which are differentially expressed between XX and XO mice, revealing secondary transcriptional changes to the alteration in X chromosome dosage. Conclusions Our results support the prediction that the mouse inactive X chromosome is largely silent, while providing a list of the genes potentially escaping X inactivation in rodents. Although the lower expression of X-linked genes in XO mice may not be relevant in the particular tissues/systems which are affected in human X chromosome monosomy, genes deregulated in XO mice are good candidates for further study in an involvement in Turner Syndrome phenotype.