Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse

Scott G. Morham; Robert Langenbach; Charles D. Loftin; Howard F. Tiano; Nectarios Vouloumanos; J. Charles Jennette; Joel F. Mahler; Kimberly D. Kluckman; Aric Ledford; Christopher A. Lee; Oliver Smithies

doi:10.1016/0092-8674(95)90125-6

Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse

Scott G. Morham, Robert Langenbach, Charles D. Loftin, Howard F. Tiano, Nectarios Vouloumanos, J. Charles Jennette, Joel F. Mahler, Kimberly D. Kluckman, Aric Ledford, Christopher A. Lee, Oliver Smithies

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

1045 Scopus citations

Abstract

The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by pro-inflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and is thought to mediate "housekeeping" functions. These two enzymes are therapeutic targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To investigate further the different physiologic roles of these isoforms, we have used homologous recombination to disrupt the mouse gene encoding COX-2 (Ptgs2). Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid. However, they develop severe nephropathy and are susceptible to peritonitis.

Original language	English
Pages (from-to)	473-482
Number of pages	10
Journal	Cell
Volume	83
Issue number	3
DOIs	https://doi.org/10.1016/0092-8674(95)90125-6
State	Published - Nov 3 1995

Bibliographical note

Funding Information:
We thank S. Bronson, D. Cook, S. Kirby, J. Krege, R. Kucherlapati, N. Maeda, and L. Marnett for review of the manuscript. We thank D. Lee, A. Staton, G. O’Neal, and Y. Zhou for invaluable technical assistance. We also appreciate the efforts of B. Gaul for necropsy assistance, as well as the efforts of the National Institute of Environmental Health Sciences histology lab. This work was supported by grants GM20069 and HL49227 from the National Institutes of Health to 0. S.; S. G. M. is an American Cancer Society fellow (#PF-3973). We gratefully acknowledge a grant from the W. M. Keck Foundation to the University of North Carolina to support work with animal models.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/0092-8674(95)90125-6

Cite this

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title = "Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse",

abstract = "The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by pro-inflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and is thought to mediate {"}housekeeping{"} functions. These two enzymes are therapeutic targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To investigate further the different physiologic roles of these isoforms, we have used homologous recombination to disrupt the mouse gene encoding COX-2 (Ptgs2). Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid. However, they develop severe nephropathy and are susceptible to peritonitis.",

author = "Morham, {Scott G.} and Robert Langenbach and Loftin, {Charles D.} and Tiano, {Howard F.} and Nectarios Vouloumanos and Jennette, {J. Charles} and Mahler, {Joel F.} and Kluckman, {Kimberly D.} and Aric Ledford and Lee, {Christopher A.} and Oliver Smithies",

note = "Funding Information: We thank S. Bronson, D. Cook, S. Kirby, J. Krege, R. Kucherlapati, N. Maeda, and L. Marnett for review of the manuscript. We thank D. Lee, A. Staton, G. O{\textquoteright}Neal, and Y. Zhou for invaluable technical assistance. We also appreciate the efforts of B. Gaul for necropsy assistance, as well as the efforts of the National Institute of Environmental Health Sciences histology lab. This work was supported by grants GM20069 and HL49227 from the National Institutes of Health to 0. S.; S. G. M. is an American Cancer Society fellow (#PF-3973). We gratefully acknowledge a grant from the W. M. Keck Foundation to the University of North Carolina to support work with animal models.",

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AU - Vouloumanos, Nectarios

AU - Jennette, J. Charles

AU - Mahler, Joel F.

AU - Kluckman, Kimberly D.

AU - Ledford, Aric

AU - Lee, Christopher A.

AU - Smithies, Oliver

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N2 - The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by pro-inflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and is thought to mediate "housekeeping" functions. These two enzymes are therapeutic targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To investigate further the different physiologic roles of these isoforms, we have used homologous recombination to disrupt the mouse gene encoding COX-2 (Ptgs2). Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid. However, they develop severe nephropathy and are susceptible to peritonitis.

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Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse

Abstract

Bibliographical note

ASJC Scopus subject areas

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