N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene.

Katsuhiko Yoshizawa, Maki Kuwata, Ayako Kawanaka, Norihisa Uehara, Takashi Yuri, Airo Tsubura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

PURPOSE: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to determine if p53 contributes to the development of MNU-induced retinal degeneration in mice. METHODS: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+) mice received the vehicle only (physiologic saline containing 0.05% acetic acid). Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were examined histologically and morphometrically to determine retinal thickness, photoreceptor cell ratio, and retinal damage ratio. RESULTS: No mice died during the experiment, but the p53 null mice treated with MNU had a statistically significant weight loss compared to the other groups. Histologically, all MNU-treated mice, regardless of p53 gene status, experienced retinal degeneration characterized by photoreceptor cell loss (the disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina. All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control. The retinal changes caused by MNU in p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence were related to a p53-independent apoptotic mechanism. CONCLUSIONS: Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

Original languageEnglish
Pages (from-to)2919-2925
Number of pages7
JournalMolecular vision
Volume15
Publication statusPublished - Jan 1 2009
Externally publishedYes

Fingerprint

Methylnitrosourea
Retinal Degeneration
p53 Genes
Photoreceptor Cells
Vertebrate Photoreceptor Cells
Retina
Retinitis Pigmentosa
Intraperitoneal Injections
Acetic Acid
Weight Loss
Animal Models
Apoptosis

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Yoshizawa, K., Kuwata, M., Kawanaka, A., Uehara, N., Yuri, T., & Tsubura, A. (2009). N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene. Molecular vision, 15, 2919-2925.

N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene. / Yoshizawa, Katsuhiko; Kuwata, Maki; Kawanaka, Ayako; Uehara, Norihisa; Yuri, Takashi; Tsubura, Airo.

In: Molecular vision, Vol. 15, 01.01.2009, p. 2919-2925.

Research output: Contribution to journalArticle

Yoshizawa, K, Kuwata, M, Kawanaka, A, Uehara, N, Yuri, T & Tsubura, A 2009, 'N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene.', Molecular vision, vol. 15, pp. 2919-2925.
Yoshizawa K, Kuwata M, Kawanaka A, Uehara N, Yuri T, Tsubura A. N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene. Molecular vision. 2009 Jan 1;15:2919-2925.
Yoshizawa, Katsuhiko ; Kuwata, Maki ; Kawanaka, Ayako ; Uehara, Norihisa ; Yuri, Takashi ; Tsubura, Airo. / N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene. In: Molecular vision. 2009 ; Vol. 15. pp. 2919-2925.
@article{3104efee2dda443f8984ea85403bd776,
title = "N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene.",
abstract = "PURPOSE: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to determine if p53 contributes to the development of MNU-induced retinal degeneration in mice. METHODS: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+) mice received the vehicle only (physiologic saline containing 0.05{\%} acetic acid). Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were examined histologically and morphometrically to determine retinal thickness, photoreceptor cell ratio, and retinal damage ratio. RESULTS: No mice died during the experiment, but the p53 null mice treated with MNU had a statistically significant weight loss compared to the other groups. Histologically, all MNU-treated mice, regardless of p53 gene status, experienced retinal degeneration characterized by photoreceptor cell loss (the disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina. All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control. The retinal changes caused by MNU in p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence were related to a p53-independent apoptotic mechanism. CONCLUSIONS: Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.",
author = "Katsuhiko Yoshizawa and Maki Kuwata and Ayako Kawanaka and Norihisa Uehara and Takashi Yuri and Airo Tsubura",
year = "2009",
month = "1",
day = "1",
language = "English",
volume = "15",
pages = "2919--2925",
journal = "Molecular Vision",
issn = "1090-0535",

}

TY - JOUR

T1 - N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene.

AU - Yoshizawa, Katsuhiko

AU - Kuwata, Maki

AU - Kawanaka, Ayako

AU - Uehara, Norihisa

AU - Yuri, Takashi

AU - Tsubura, Airo

PY - 2009/1/1

Y1 - 2009/1/1

N2 - PURPOSE: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to determine if p53 contributes to the development of MNU-induced retinal degeneration in mice. METHODS: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+) mice received the vehicle only (physiologic saline containing 0.05% acetic acid). Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were examined histologically and morphometrically to determine retinal thickness, photoreceptor cell ratio, and retinal damage ratio. RESULTS: No mice died during the experiment, but the p53 null mice treated with MNU had a statistically significant weight loss compared to the other groups. Histologically, all MNU-treated mice, regardless of p53 gene status, experienced retinal degeneration characterized by photoreceptor cell loss (the disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina. All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control. The retinal changes caused by MNU in p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence were related to a p53-independent apoptotic mechanism. CONCLUSIONS: Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

AB - PURPOSE: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to determine if p53 contributes to the development of MNU-induced retinal degeneration in mice. METHODS: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+) mice received the vehicle only (physiologic saline containing 0.05% acetic acid). Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were examined histologically and morphometrically to determine retinal thickness, photoreceptor cell ratio, and retinal damage ratio. RESULTS: No mice died during the experiment, but the p53 null mice treated with MNU had a statistically significant weight loss compared to the other groups. Histologically, all MNU-treated mice, regardless of p53 gene status, experienced retinal degeneration characterized by photoreceptor cell loss (the disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina. All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control. The retinal changes caused by MNU in p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence were related to a p53-independent apoptotic mechanism. CONCLUSIONS: Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

UR - http://www.scopus.com/inward/record.url?scp=77649248174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649248174&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 2919

EP - 2925

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -