Transcriptomics,Genomics

Dataset Information

21

Meiotic Consequences of Aneuploidy: Mouse Models of Down Syndrome


ABSTRACT: Aneuploidy, and especially the presence of unpaired chromosomal axes during meiosis, can cause infertility. However, it is not known if extra, unpaired autosomal chromosome segments acquire characteristic protein modifications and undergo transcriptional silencing (meiotic silencing of unpaired chromatin, or MSUC) similar to the unpaired regions of the X and Y chromosomes during spermatogenesis. We used three mouse models of Down syndrome, involving either an extra chromosome or translocation trisomy, to test requirements and consequences of meiotic protein modification and gene silencing in spermatocytes. These models reveal that copy number alone is not sufficient for up-regulation of genes in the trisomic interval, and that MSUC-promoting modifications are not sufficient for down-regulation of genes that reside in unpaired chromatin during meiosis. The position of a trisomic region relative to a centromere, the pairing status of the centromere, and the physical extent of the unpaired chromosomal region all affected assembly of meiotic protein modifications typical of MSUC. One key determinant to modification of unpaired chromatin and infertility in trisomy male mice appears to be proximity of unpaired chromatin to a centromere. Furthermore, the presence of an extra, unpaired centromere, but not translocation trisomy, causes global misregulation of transcription in spermatocytes. Thus, neither trisomy per se, nor chromatin modifications of unpaired chromosomal segments, have major effects on gene expression or meiotic success, but an intact unpaired chromosome has profoundly negative effects on meiotic gene expression. Overall design: Three biological replicate RNA samples from enriched male germ cells from two mouse Down Syndrome mouse models, Ts1Cje and Ts65Dn, and diploid wild-type littermate controls, WT, from two time points, 16-17 and 19-20 days post partum(dpp), were assayed for gene expression using Illumina MouseWG-6 v1.1 BeadArrays.

INSTRUMENT(S): Illumina mouse-6 v1.1 expression beadchip [Array_Address_Id version]

SUBMITTER: Laura G Reinholdt   

PROVIDER: GSE13123 | GEO | 2008-10-11

SECONDARY ACCESSION(S): PRJNA109663

REPOSITORIES: GEO

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Publications

Meiotic behavior of aneuploid chromatin in mouse models of Down syndrome.

Reinholdt Laura G LG   Czechanski Anne A   Kamdar Sonya S   King Benjamin L BL   Sun Fengyun F   Handel Mary Ann MA  

Chromosoma 20090729 6


Aneuploidy, which leads to unpaired chromosomal axes during meiosis, is frequently accompanied by infertility. We previously showed, using three mouse models of Down syndrome, that it is an extra chromosome, but not extra gene dose, that is associated with male infertility and virtual absence of post-meiotic gem cells. Here, we test the hypothesis that aneuploid segments are differentially modified and expressed during meiosis, depending on whether they are present as an extra chromosome or not.  ...[more]

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