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Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling.

Lai CW, Chen HL, Tsai TC, Chu TW, Yang SH, Chong KY, Chen CM - Sci Rep (2016)

Bottom Line: However, the mechanism of sexually dimorphic expression is still not fully understood.In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver, and the expression was activated by testosterone during puberty.The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator, and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.

ABSTRACT
Sexually dimorphic gene expression is commonly found in the liver, and many of these genes are linked to different incidences of liver diseases between sexes. However, the mechanism of sexually dimorphic expression is still not fully understood. In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver, and the expression was activated by testosterone during puberty. The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator, and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation. Through this de novo sexually dimorphic expression of the transgene, the Akr1A1(eGFP) mouse provides a useful model to study the mechanisms and the dynamic changes of sexually dimorphic gene expression during either development or pathogenesis of the liver.

No MeSH data available.


Related in: MedlinePlus

Sex hormones are crucial for the formation of the sexually dimorphic EGFP expression in the Akr1A1eGFP/+ mouse liver during puberty.(A) The experimental schedule of Tg mice that underwent gonadectomy at 4 or 8 weeks of age and were sacrificed at 12 weeks of age for IHC analysis. (B) IHC of EGFP expression in the livers of intact Tg mice and mice that had undergone gonadectomy at 4 or 8 weeks of age. Scale bar: 500 μm. (C) The quantification of the EGFP expression area in IHC sections ([EGFP area (brown color)/total area] × 100%). The bars show the mean ± s.e.m. of five animals per group (n = 5); data were analyzed by one-tailed Student’s t-test; **P < 0.01 vs. the female group with the same treatment.
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f5: Sex hormones are crucial for the formation of the sexually dimorphic EGFP expression in the Akr1A1eGFP/+ mouse liver during puberty.(A) The experimental schedule of Tg mice that underwent gonadectomy at 4 or 8 weeks of age and were sacrificed at 12 weeks of age for IHC analysis. (B) IHC of EGFP expression in the livers of intact Tg mice and mice that had undergone gonadectomy at 4 or 8 weeks of age. Scale bar: 500 μm. (C) The quantification of the EGFP expression area in IHC sections ([EGFP area (brown color)/total area] × 100%). The bars show the mean ± s.e.m. of five animals per group (n = 5); data were analyzed by one-tailed Student’s t-test; **P < 0.01 vs. the female group with the same treatment.

Mentions: To determine whether the sex hormones, which are released during puberty, activated the sexually dimorphic EGFP expression in the mouse livers, we performed gonadectomies in the male and female Tg mice pre-puberty (4 weeks old) and post-puberty (8 weeks old) and then analyzed the EGFP expression at maturity (12 weeks old) (Fig. 5A). The results showed that the sexually dimorphic expression of EGFP was abolished when the operation was performed at 4 weeks old, but there was no change between the intact mice and the mice that underwent gonadectomy at 8 weeks old (Fig. 5B,C). These results indicate that the sex hormones and the timing of their secretion are crucial for the sexually dimorphic expression of EGFP in the Tg mouse livers.


Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling.

Lai CW, Chen HL, Tsai TC, Chu TW, Yang SH, Chong KY, Chen CM - Sci Rep (2016)

Sex hormones are crucial for the formation of the sexually dimorphic EGFP expression in the Akr1A1eGFP/+ mouse liver during puberty.(A) The experimental schedule of Tg mice that underwent gonadectomy at 4 or 8 weeks of age and were sacrificed at 12 weeks of age for IHC analysis. (B) IHC of EGFP expression in the livers of intact Tg mice and mice that had undergone gonadectomy at 4 or 8 weeks of age. Scale bar: 500 μm. (C) The quantification of the EGFP expression area in IHC sections ([EGFP area (brown color)/total area] × 100%). The bars show the mean ± s.e.m. of five animals per group (n = 5); data were analyzed by one-tailed Student’s t-test; **P < 0.01 vs. the female group with the same treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834580&req=5

f5: Sex hormones are crucial for the formation of the sexually dimorphic EGFP expression in the Akr1A1eGFP/+ mouse liver during puberty.(A) The experimental schedule of Tg mice that underwent gonadectomy at 4 or 8 weeks of age and were sacrificed at 12 weeks of age for IHC analysis. (B) IHC of EGFP expression in the livers of intact Tg mice and mice that had undergone gonadectomy at 4 or 8 weeks of age. Scale bar: 500 μm. (C) The quantification of the EGFP expression area in IHC sections ([EGFP area (brown color)/total area] × 100%). The bars show the mean ± s.e.m. of five animals per group (n = 5); data were analyzed by one-tailed Student’s t-test; **P < 0.01 vs. the female group with the same treatment.
Mentions: To determine whether the sex hormones, which are released during puberty, activated the sexually dimorphic EGFP expression in the mouse livers, we performed gonadectomies in the male and female Tg mice pre-puberty (4 weeks old) and post-puberty (8 weeks old) and then analyzed the EGFP expression at maturity (12 weeks old) (Fig. 5A). The results showed that the sexually dimorphic expression of EGFP was abolished when the operation was performed at 4 weeks old, but there was no change between the intact mice and the mice that underwent gonadectomy at 8 weeks old (Fig. 5B,C). These results indicate that the sex hormones and the timing of their secretion are crucial for the sexually dimorphic expression of EGFP in the Tg mouse livers.

Bottom Line: However, the mechanism of sexually dimorphic expression is still not fully understood.In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver, and the expression was activated by testosterone during puberty.The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator, and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.

ABSTRACT
Sexually dimorphic gene expression is commonly found in the liver, and many of these genes are linked to different incidences of liver diseases between sexes. However, the mechanism of sexually dimorphic expression is still not fully understood. In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver, and the expression was activated by testosterone during puberty. The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator, and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation. Through this de novo sexually dimorphic expression of the transgene, the Akr1A1(eGFP) mouse provides a useful model to study the mechanisms and the dynamic changes of sexually dimorphic gene expression during either development or pathogenesis of the liver.

No MeSH data available.


Related in: MedlinePlus