Histopathology in Mouse Metabolic Investigations

Mark, Manuel; Teletin, Marius; Antal, Cristina; Wendling, Olivia; Auwerx, Johan; Heikkinen, Sami; Khetchoumian, Konstantin; Argmann, Carmen; Dgheem, Mounzer

doi:10.1002/0471142727.mb29b04s78

Cited by 31 publications

(38 citation statements)

References 19 publications

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“…After dehydration and embedding in paraffin, 5-mm sections were prepared and stained with hematoxylin and eosin as described (Mark et al 2007). Apoptotic cell detection was performed in testes fixed with 4% paraformaldehyde using the Deadend Fluorometric TUNEL system according to the supplier's instructions (Promega).…”

Section: Histological Analysismentioning

confidence: 99%

Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice

Kumar¹,

Bourbon²,

Massy³

2010

Genes Dev.

197

321

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Meiotic recombination is initiated by the programmed induction of DNA double-strand breaks (DSBs) catalyzed by the evolutionarily conserved Spo11 protein. Studies in yeast have shown that DSB formation requires several other proteins, the role and conservation of which remain unknown. Here we show that two of these Saccharomyces cerevisiae proteins, Mei4 and Rec114, are evolutionarily conserved in most eukaryotes. Mei4 À/À mice are deficient in meiotic DSB formation, thus showing the functional conservation of Mei4 in mice. Cytological analyses reveal that, in mice, MEI4 is localized in discrete foci on the axes of meiotic chromosomes that do not overlap with DMC1 and RPA foci. We thus propose that MEI4 acts as a structural component of the DSB machinery that ensures meiotic DSB formation on chromosome axes. We show that mouse MEI4 and REC114 proteins interact directly, and we identify conserved motifs as required for this interaction. Finally, the unexpected, concomitant absence of Mei4 and Rec114, as well as of Mnd1, Hop2, and Dmc1, in some eukaryotic species (particularly Neurospora crassa, Drosophila melanogaster, and Caenorhabditis elegans) suggests the existence of Mei4-Rec114-dependent and Mei4-Rec114-independent mechanisms for DSB formation, and a functional relationship between the chromosome axis and DSB formation. In sexually reproducing organisms, the chromosome content of diploid germ cells must be halved during gamete formation. This is achieved by the specialized meiotic cycle composed of one replication phase followed by two divisions, thereby leading to the formation of four haploid gametes from a diploid cell. During the first division (the reductional division), homologous chromosomes segregate from each other, whereas during the second division, sister chromatids segregate. The reductional division is unique to meiotic cells and requires specialized mechanisms to connect homologous chromosomes for their proper orientation at metaphase I and faithful separation by the segregation machinery. In most eukaryotes, these connections are established by crossovers (COs), which are reciprocal recombination events between homologous chromosomes, visualized in the cell as chiasmata (Petronczki et al. 2003). The mechanical role of COs implies a precise regulation of the frequency of these events, at least one per chromosome. These recombination events, in addition to ensuring the mechanism of reductional segregation, also have evolutionary consequences as they increase genome diversity (Coop and Przeworski 2007).The molecular mechanism of CO formation has been analyzed in details in Saccharomyces cerevisiae and Schizosaccharomyces pombe (Hunter 2007), and several of the main properties are conserved in mammals (Handel and Schimenti 2010) and other eukaryotes. Meiotic recombination is initiated by the formation of DNA doublestrand breaks (DSBs). DSBs are repaired by homologous recombination using the homologous chromosome as a template, leading to a gene conversion either without CO (NCO) or with CO (Baud...

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Section: Histological Analysismentioning

confidence: 99%

Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice

Kumar¹,

Bourbon²,

Massy³

2010

Genes Dev.

197

321

View full text Add to dashboard Cite

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“…H&E staining was performed as described previously (92). Antibodies against F4/80 (Abcam) were used for immunohistochemistry to detect macrophages.…”

Section: Tgr5mentioning

confidence: 99%

TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation

Perino¹,

Pols²,

Nomura³

et al. 2014

J. Clin. Invest.

182

128

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“…Staining of histological sections with haematoxylin and eosin, periodic acid Schiff (PAS), osmium tetroxide, toluidine blue and oil red O, and histochemical detection of cholesterol esters were as described (Mark et al 2007). For detection of apoptotic cells (TUNEL assays), testis samples were fixed in 4% (w/v) paraformaldehyde in PBS for 16 h at 4 8C, then embedded in paraffin.…”

Section: Histology Histochemistry and Tunel Assaysmentioning

confidence: 99%

Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation

Vernet¹,

Dennefeld²,

Klopfenstein³

et al. 2008

Reproduction

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Somatic, targeted inactivation of the retinoid X receptor beta gene (Rxrb) in Sertoli cells (SC; yielding Rxrb SerK/K mutants) leads to failure of spermatid release, accumulation of cholesterol esters and, subsequently, testis degeneration. These abnormalities are identical, in their nature and kinetics, to those observed upon inactivating Rxrb in the whole organism, thereby demonstrating that all reproductive functions of RXRB are carried out in SC. The Rxrb SerK/K testis degeneration is a consequence of a cholesterol ester cell overload occurring in SC in response to reduced ABCA1-and SCARB1-mediated cholesterol efflux. The failure of spermiation was also reported in mice lacking the retinoic acid (RA) receptor-a (RARA) in SC (Rara SerK/K mutants) and represents, in addition, a feature of vitamin A deficiency that can be readily induced in mice lacking the lecithin:retinol acyltransferase (Lrat K/K mutants). Altogether, these findings support the conclusion that RXRB heterodimerized with a RA-liganded RARA transduces signals required in SC for spermatid release.

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Histopathology in Mouse Metabolic Investigations

Cited by 31 publications

References 19 publications

Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice

Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice

TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation

Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation

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