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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

The change in expression of EGFP during the development of the liver in male and female Akr1A1eGFP/+ mice.IHC staining (A) and western blot (B) analysis of the EGFP protein that was expressed in the livers of 1-, 3-, 5- and 7-week-old male and female Tg mice. Scale bar: 100 μm. (C) The quantification of EGFP expression was determined by western blot. β-actin expression was used as an internal control. 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 at the age of 7 weeks.
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f4: The change in expression of EGFP during the development of the liver in male and female Akr1A1eGFP/+ mice.IHC staining (A) and western blot (B) analysis of the EGFP protein that was expressed in the livers of 1-, 3-, 5- and 7-week-old male and female Tg mice. Scale bar: 100 μm. (C) The quantification of EGFP expression was determined by western blot. β-actin expression was used as an internal control. 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 at the age of 7 weeks.

Mentions: Gene expression in the liver is varied and influenced by metabolic changes and liver function shifts during maturation of the liver. Thus, the EGFP expression in the livers from male and female Tg mice was evaluated at different ages. At 1 week of age, when the mice were still breastfeeding, the EGFP showed neither sex-biased expression nor zonal expression in the hepatic lobule. At the ages of 3 and 5 weeks, when the mice were weaned and at the initial stage of puberty, respectively, zonal expression of EGFP was observed, but there was still no sex-biased expression in the males and females. During late puberty (7 weeks old), sexually dimorphic expression was present (Fig. 4A and Supplementary Fig. S2), and similar results were also shown by in vivo EGFP fluorescence imaging (Supplementary Fig. S3). Western blot analysis of EGFP in the Tg mouse livers showed that EGFP expression showed no significant difference between males and females during 1 to 5 weeks of age, but at 7 weeks, the EGFP expression in the livers of males was significantly increased compared to the livers of female mice (P = 0.006) (Fig. 4B,C). These results indicate that the sexually dimorphic expression of the pCAG-eGFP transgene in the Tg mouse liver was similar to endogenous sexually dimorphic genes12, which present male-biased and up-regulated expression after puberty.


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)

The change in expression of EGFP during the development of the liver in male and female Akr1A1eGFP/+ mice.IHC staining (A) and western blot (B) analysis of the EGFP protein that was expressed in the livers of 1-, 3-, 5- and 7-week-old male and female Tg mice. Scale bar: 100 μm. (C) The quantification of EGFP expression was determined by western blot. β-actin expression was used as an internal control. 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 at the age of 7 weeks.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: The change in expression of EGFP during the development of the liver in male and female Akr1A1eGFP/+ mice.IHC staining (A) and western blot (B) analysis of the EGFP protein that was expressed in the livers of 1-, 3-, 5- and 7-week-old male and female Tg mice. Scale bar: 100 μm. (C) The quantification of EGFP expression was determined by western blot. β-actin expression was used as an internal control. 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 at the age of 7 weeks.
Mentions: Gene expression in the liver is varied and influenced by metabolic changes and liver function shifts during maturation of the liver. Thus, the EGFP expression in the livers from male and female Tg mice was evaluated at different ages. At 1 week of age, when the mice were still breastfeeding, the EGFP showed neither sex-biased expression nor zonal expression in the hepatic lobule. At the ages of 3 and 5 weeks, when the mice were weaned and at the initial stage of puberty, respectively, zonal expression of EGFP was observed, but there was still no sex-biased expression in the males and females. During late puberty (7 weeks old), sexually dimorphic expression was present (Fig. 4A and Supplementary Fig. S2), and similar results were also shown by in vivo EGFP fluorescence imaging (Supplementary Fig. S3). Western blot analysis of EGFP in the Tg mouse livers showed that EGFP expression showed no significant difference between males and females during 1 to 5 weeks of age, but at 7 weeks, the EGFP expression in the livers of males was significantly increased compared to the livers of female mice (P = 0.006) (Fig. 4B,C). These results indicate that the sexually dimorphic expression of the pCAG-eGFP transgene in the Tg mouse liver was similar to endogenous sexually dimorphic genes12, which present male-biased and up-regulated expression after puberty.

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