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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 pCAG-eGFP transgenic mice were generated by pronuclear microinjection.(A) The structure of the pCAG-eGFP transgene. (B) Live imaging of the EGFP fluorescence in Akr1A1eGFP/+ and WT mice. (C) The in vivo EGFP fluorescence imaging of nine organs in the male and female Akr1A1eGFP/eGFP and Akr1A1eGFP/+ mice. Br: brain, He: heart, Lu: lung, Li: liver, Ke: kidney, Sp: spleen, Ov: ovary, Ut: uterus and Te: testis. (D) The chromosome FISH of the sexually dimorphic EGFP-expressing mouse line. The arrowhead shows the transgenic signals in the chromosome.
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f1: The pCAG-eGFP transgenic mice were generated by pronuclear microinjection.(A) The structure of the pCAG-eGFP transgene. (B) Live imaging of the EGFP fluorescence in Akr1A1eGFP/+ and WT mice. (C) The in vivo EGFP fluorescence imaging of nine organs in the male and female Akr1A1eGFP/eGFP and Akr1A1eGFP/+ mice. Br: brain, He: heart, Lu: lung, Li: liver, Ke: kidney, Sp: spleen, Ov: ovary, Ut: uterus and Te: testis. (D) The chromosome FISH of the sexually dimorphic EGFP-expressing mouse line. The arrowhead shows the transgenic signals in the chromosome.

Mentions: A 3,253 bp pCAG-eGFP expression vector (Fig. 1A) was used to generate Tg mice with strong and ubiquitously expressed EGFP (Fig. 1B). One of the Tg mouse lines showed an interesting expression profile, in which the transgene exhibited sexually dimorphic expression in the liver but only small or no differences between the sexes in other organs, including the brain, heart, lung, kidney, spleen and gonads (Fig. 1C).


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 pCAG-eGFP transgenic mice were generated by pronuclear microinjection.(A) The structure of the pCAG-eGFP transgene. (B) Live imaging of the EGFP fluorescence in Akr1A1eGFP/+ and WT mice. (C) The in vivo EGFP fluorescence imaging of nine organs in the male and female Akr1A1eGFP/eGFP and Akr1A1eGFP/+ mice. Br: brain, He: heart, Lu: lung, Li: liver, Ke: kidney, Sp: spleen, Ov: ovary, Ut: uterus and Te: testis. (D) The chromosome FISH of the sexually dimorphic EGFP-expressing mouse line. The arrowhead shows the transgenic signals in the chromosome.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: The pCAG-eGFP transgenic mice were generated by pronuclear microinjection.(A) The structure of the pCAG-eGFP transgene. (B) Live imaging of the EGFP fluorescence in Akr1A1eGFP/+ and WT mice. (C) The in vivo EGFP fluorescence imaging of nine organs in the male and female Akr1A1eGFP/eGFP and Akr1A1eGFP/+ mice. Br: brain, He: heart, Lu: lung, Li: liver, Ke: kidney, Sp: spleen, Ov: ovary, Ut: uterus and Te: testis. (D) The chromosome FISH of the sexually dimorphic EGFP-expressing mouse line. The arrowhead shows the transgenic signals in the chromosome.
Mentions: A 3,253 bp pCAG-eGFP expression vector (Fig. 1A) was used to generate Tg mice with strong and ubiquitously expressed EGFP (Fig. 1B). One of the Tg mouse lines showed an interesting expression profile, in which the transgene exhibited sexually dimorphic expression in the liver but only small or no differences between the sexes in other organs, including the brain, heart, lung, kidney, spleen and gonads (Fig. 1C).

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