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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

Histological appearance of the kidney, liver and abdominal aorta in WT and GMF-TG mice(A-F) These photographs show an overview of the hematoxylin-eosin (HE) (A and D), periodic acid–schiff (PAS) (B and E), and Masson trichrome (MTC) (C and F) stained kidney sections in the WT (A-C) and GMF-TG (D-F) mice at 30 weeks. (G-L) These photographs show an overview of the HE (G and J), PAS (H and K), and MTC (I and L) stained liver sections in the WT (G-I) and GMF-TG (J-L) mice at 30 weeks. (M-R) These photographs show an overview of the HE (M and P), PAS (N and Q), and MTC (O and R) stained abdominal aorta sections in the WT (M-O) and GMF-TG (P-R) mice at 30 weeks. These findings revealed no histological differences between the WT and GMF-TG mice. Magnifications: ×100, Scale Bar = 200 μm.
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Figure 5: Histological appearance of the kidney, liver and abdominal aorta in WT and GMF-TG mice(A-F) These photographs show an overview of the hematoxylin-eosin (HE) (A and D), periodic acid–schiff (PAS) (B and E), and Masson trichrome (MTC) (C and F) stained kidney sections in the WT (A-C) and GMF-TG (D-F) mice at 30 weeks. (G-L) These photographs show an overview of the HE (G and J), PAS (H and K), and MTC (I and L) stained liver sections in the WT (G-I) and GMF-TG (J-L) mice at 30 weeks. (M-R) These photographs show an overview of the HE (M and P), PAS (N and Q), and MTC (O and R) stained abdominal aorta sections in the WT (M-O) and GMF-TG (P-R) mice at 30 weeks. These findings revealed no histological differences between the WT and GMF-TG mice. Magnifications: ×100, Scale Bar = 200 μm.

Mentions: Next, we examined aging-related changes in the tissue structure. Degenerative changes in skin tissue are readily visible, so they can be detected easily [27]. Decreased hair regrowth has often been reported in prematurely aged mice [25–27]. Because hair growth assays can be employed to monitor degenerative changes without adversely affecting the mice, we employed them to investigate the influence of aging on skin tissue. When dorsal segments of skin were shaved on age-matched mice, the GMF-TG mice showed sparse hair regrowth after 15-days. In contrast, at the same age, the wild-type mice displayed robust hair regrowth (Figure 4A). The hair regrowth ratio significantly declined in the GMF-TG mice at 10, 60 and 80 weeks, compared with the wild-type mice at the same age (Figure 4B). In the kidney, liver, and abdominal aorta at 30 weeks, there were no histologically detectable changes between the GMF-TG and wild-type mice, as indicated in Figure 5. These results suggested that the GMF-TG mice developed mild premature aging phenotypes.


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)

Histological appearance of the kidney, liver and abdominal aorta in WT and GMF-TG mice(A-F) These photographs show an overview of the hematoxylin-eosin (HE) (A and D), periodic acid–schiff (PAS) (B and E), and Masson trichrome (MTC) (C and F) stained kidney sections in the WT (A-C) and GMF-TG (D-F) mice at 30 weeks. (G-L) These photographs show an overview of the HE (G and J), PAS (H and K), and MTC (I and L) stained liver sections in the WT (G-I) and GMF-TG (J-L) mice at 30 weeks. (M-R) These photographs show an overview of the HE (M and P), PAS (N and Q), and MTC (O and R) stained abdominal aorta sections in the WT (M-O) and GMF-TG (P-R) mice at 30 weeks. These findings revealed no histological differences between the WT and GMF-TG mice. Magnifications: ×100, Scale Bar = 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Histological appearance of the kidney, liver and abdominal aorta in WT and GMF-TG mice(A-F) These photographs show an overview of the hematoxylin-eosin (HE) (A and D), periodic acid–schiff (PAS) (B and E), and Masson trichrome (MTC) (C and F) stained kidney sections in the WT (A-C) and GMF-TG (D-F) mice at 30 weeks. (G-L) These photographs show an overview of the HE (G and J), PAS (H and K), and MTC (I and L) stained liver sections in the WT (G-I) and GMF-TG (J-L) mice at 30 weeks. (M-R) These photographs show an overview of the HE (M and P), PAS (N and Q), and MTC (O and R) stained abdominal aorta sections in the WT (M-O) and GMF-TG (P-R) mice at 30 weeks. These findings revealed no histological differences between the WT and GMF-TG mice. Magnifications: ×100, Scale Bar = 200 μm.
Mentions: Next, we examined aging-related changes in the tissue structure. Degenerative changes in skin tissue are readily visible, so they can be detected easily [27]. Decreased hair regrowth has often been reported in prematurely aged mice [25–27]. Because hair growth assays can be employed to monitor degenerative changes without adversely affecting the mice, we employed them to investigate the influence of aging on skin tissue. When dorsal segments of skin were shaved on age-matched mice, the GMF-TG mice showed sparse hair regrowth after 15-days. In contrast, at the same age, the wild-type mice displayed robust hair regrowth (Figure 4A). The hair regrowth ratio significantly declined in the GMF-TG mice at 10, 60 and 80 weeks, compared with the wild-type mice at the same age (Figure 4B). In the kidney, liver, and abdominal aorta at 30 weeks, there were no histologically detectable changes between the GMF-TG and wild-type mice, as indicated in Figure 5. These results suggested that the GMF-TG mice developed mild premature aging phenotypes.

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