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. 2008 Feb 19;105(7):2433-8.
doi: 10.1073/pnas.0712029105. Epub 2008 Feb 11.

Sterility and absence of histopathological defects in nonreproductive organs of a mouse ERbeta-null mutant

Maria Cristina Antal  1 , Andrée Krust, Pierre Chambon, Manuel Mark
Affiliations

Sterility and absence of histopathological defects in nonreproductive organs of a mouse ERbeta-null mutant

Maria Cristina Antal et al. Proc Natl Acad Sci U S A. .

Abstract

Estrogen signaling is mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). Although a consensus has now been reached concerning many physiological functions of ERalpha, those of ERbeta are still controversial: When housed and examined in two distant laboratories, mice originating from the same initial ERbeta mutant exhibited widely different phenotypes, which were themselves different from the phenotype of another ERbeta mutant previously generated in our laboratory. Because, in addition to a knockout insertion in exon 3, all these mouse mutants displayed alternative splicing transcripts, we have now constructed a ERbeta mouse mutant (ERbeta(ST)(L-/L-)) in which exon 3 was cleanly deleted by Cre/LoxP-mediated excision and was devoid of any transcript downstream of exon 3. Both females and males were sterile. The histology of the ovary was mildly affected, and no histological defects were detected in other organs, neither in females nor in males. Our present results, which are in contrast with previously published data, suggest that, with the notable exception of male and female reproduction, ERbeta is not required in the mouse for the development and homeostasis of the major body systems.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Normal morphology and cell proliferation in the ventral prostate of 16-month-old ERβSTL−/L− mice. (a–d) Hematoxylin and eosin-stained sections of ventral prostate. (c and d) Higher magnification of functionally hyperplastic alveoli. (e–h) Immunostaining for detection of the cell proliferation marker Ki67 in ventral prostate. Arrows point to Ki67-positive epithelial cells (red signals). (g and h) Enlargement of the black frames from e and f, respectively. E, prostatic epithelium; M, smooth muscle; VP1 and VP2, alveoli without and with functional hyperplasia, respectively. Four males of each genotype were used in each type of assay. (Scale bar: a and b, 500 μm; c–f, 50 μm.)
Fig. 2.
Fig. 2.
The ERβSTL−/L− mutation does not alter architecture and neuronal density of the somatosensory cortex and does not elicit astrocytosis in 16-month-old mice. (a–d) Coronal sections at similar levels of the brains of WT and ERβSTL−/L− males. (e–h) Immunodetection of GFAP (red signals) and DAPI counterstain (blue nuclei) in the paraventricular nucleus (e and f) and amygdala (g and h). C, cerebral cortex. Five males of each genotype were used for histology. (Scale bar: a and b, 500 μm; c and d, 250 μm; e–h, 30 μm.)
Fig. 3.
Fig. 3.
Absence of myeloproliferation in 16- to 19-month-old ERβSTL−/L− mice. (a–d) Sections of hematopoietic compartment of the spleen (a and b) and bone marrow (c and d) of ERβSTL−/L− females (hematoxylin and eosin). Myeloid precursors (MP) appear as large cells, containing (i) a large, pale-stained nucleus displaying prominent nucleoli and a finely granular chromatin and (ii) a relatively low abundance of lightly stained cytoplasm. In contrast, erythroid precursors (EP) are medium- to small-sized cells, with dark nuclei and low amount of darkly stained cytoplasm. MK, megakaryocyte. Nine mice of each sex and genotype were used for histology. (Scale bar: 8 μm.)
Fig. 4.
Fig. 4.
Normal morphology of the lung and heart of 16- to 19-month-old ERβSTL−/L− mice. (a and b) Normal cellular composition of the lung of ERβSTL−/L− females (hematoxylin and eosin). (c and d) Normal cardiomyocyte size and intercellular spaces in the heart of ERβSTL−/L− males (modified Mallory's trichrome). (e and f) Normal pattern of f-actin distribution in the sarcomeres of ERβSTL−/L−hearts; sections are stained with FITC-conjugated phalloidin. (g and h) Normal structure of intercalated discs in ERβSTL−/L− hearts; transmission electron microscopy. (i) Normal mean alveolar surface in ERβSTL−/L− female lungs (arbitrary units; pixels × 103; means ± SEM). (j) Normal mean left ventricular wall surface in ERβSTL−/L− male heart (arbitrary units; pixel × 105; means ± SEM). A, alveolar lumen; CM, cardiomyocytes; E, endothelial cell; I and Z, I and Z bands, respectively; ID, intercalated disk; IS, intercellular spaces; M, mitochondria; P1 and P2, type 1 and 2 pneumocytes, respectively. Nineteen-month-old females of each genotype were used, 10 for histological analysis and 5 for alveolar surface measurement; 16-month-old males of each genotype were used, 8 for evaluation of cardiomyocytes size and left ventricle wall surface, 5 for f-actin staining and 3 for electron microscopy. (Scale bar: a and b, 40 μm; c–f, 100 μm; g and h, 2 μm.)
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References

    1. Couse JF, Korach KS. Estrogen receptor null mice: What have we learned and where will they lead us? Endocrine Rev. 1999;20:358–417. - PubMed
    1. Mueller SO, Korach KS. Estrogen receptors and endocrine diseases: Lessons from estrogen receptor knockout mice. Curr Opin Pharmacol. 2001;1:613–619. - PubMed
    1. Korach KS, et al. Update on animal models developed for analyses of estrogen receptor biological activity. J Steroid Biochem Mol Biol. 2003;86:387–391. - PubMed
    1. Hewitt SC, Harrell JC, Korach KS. Lessons in estrogen biology from knockout and transgenic animals. Annu Rev Physiol. 2005;67:285–308. - PubMed
    1. Walter P, et al. Cloning of the human estrogen receptor cDNA. Proc Natl Acad Sci USA. 1985;82:7889–7893. - PMC - PubMed

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