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Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

Imai R, Asai K, Hanai J, Takenaka M - Aging (Albany NY) (2015)

Bottom Line: The GMF-TG mice exhibited appearance phenotypes associated with premature aging.The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies.The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks.

View Article: PubMed Central - PubMed

Affiliation: Clinical Nutrition and Internal Medicine, Kobe Women's University, Kobe 654-8585, Japan.

ABSTRACT
Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

No MeSH data available.


Related in: MedlinePlus

Preparation of transgenic mice overexpressing GMF (GMF-TG)(A) This figure shows the construct used to prepare the transgenic mice. The construct was prepared by cloning the coding region of GMF (97–915 bp) in a pCAGGS vector. (B) This figure shows that the gene expression of GMF in the kidney of the GMF-TG mice was significantly higher (about 7-fold) than that of the wild-type (WT) mice. The data is shown as means ± S.E. (WT; n=3, GMF-TG; n=3). *; P < 0.05 vs. WT mice.
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Figure 1: Preparation of transgenic mice overexpressing GMF (GMF-TG)(A) This figure shows the construct used to prepare the transgenic mice. The construct was prepared by cloning the coding region of GMF (97–915 bp) in a pCAGGS vector. (B) This figure shows that the gene expression of GMF in the kidney of the GMF-TG mice was significantly higher (about 7-fold) than that of the wild-type (WT) mice. The data is shown as means ± S.E. (WT; n=3, GMF-TG; n=3). *; P < 0.05 vs. WT mice.

Mentions: It is considered that GMF is normally expressed in the brain in a tissue-specific manner [9, 10]. However, GMF is also induced ectopically in renal proximal tubules by proteinuria [7, 8]. In order to analyze the roles of a previously unknown GMF overexpression in non-brain tissue, we first created transgenic mice overexpressing GMF (GMF-TG mice), as described in the ‘Materials and Methods’ section (Figure 1A).


Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

Imai R, Asai K, Hanai J, Takenaka M - Aging (Albany NY) (2015)

Preparation of transgenic mice overexpressing GMF (GMF-TG)(A) This figure shows the construct used to prepare the transgenic mice. The construct was prepared by cloning the coding region of GMF (97–915 bp) in a pCAGGS vector. (B) This figure shows that the gene expression of GMF in the kidney of the GMF-TG mice was significantly higher (about 7-fold) than that of the wild-type (WT) mice. The data is shown as means ± S.E. (WT; n=3, GMF-TG; n=3). *; P < 0.05 vs. WT mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543038&req=5

Figure 1: Preparation of transgenic mice overexpressing GMF (GMF-TG)(A) This figure shows the construct used to prepare the transgenic mice. The construct was prepared by cloning the coding region of GMF (97–915 bp) in a pCAGGS vector. (B) This figure shows that the gene expression of GMF in the kidney of the GMF-TG mice was significantly higher (about 7-fold) than that of the wild-type (WT) mice. The data is shown as means ± S.E. (WT; n=3, GMF-TG; n=3). *; P < 0.05 vs. WT mice.
Mentions: It is considered that GMF is normally expressed in the brain in a tissue-specific manner [9, 10]. However, GMF is also induced ectopically in renal proximal tubules by proteinuria [7, 8]. In order to analyze the roles of a previously unknown GMF overexpression in non-brain tissue, we first created transgenic mice overexpressing GMF (GMF-TG mice), as described in the ‘Materials and Methods’ section (Figure 1A).

Bottom Line: The GMF-TG mice exhibited appearance phenotypes associated with premature aging.The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies.The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks.

View Article: PubMed Central - PubMed

Affiliation: Clinical Nutrition and Internal Medicine, Kobe Women's University, Kobe 654-8585, Japan.

ABSTRACT
Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

No MeSH data available.


Related in: MedlinePlus