Impact of estrogen receptor deficiency on disease expression in the NZM2410 lupus prone mouse

John L. Svenson; Jackie EuDaly; Phil Ruiz; Kenneth S. Korach; Gary S. Gilkeson

doi:10.1016/j.clim.2008.03.508

Impact of estrogen receptor deficiency on disease expression in the NZM2410 lupus prone mouse

John L. Svenson, Jackie EuDaly, Phil Ruiz, Kenneth S. Korach, Gary S. Gilkeson

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Abstract

Systemic lupus erythematosus (SLE) occurs nine times more often in females than males. The purpose of this study was to determine the impact of estrogen receptor (ER) null genotypes on disease in lupus prone NZM2410 (NZM) and MRL/lpr mice, as a method to define the role of estrogen receptor signaling in lupus. ERα deficient NZM females, but not males, had significantly prolonged survival, reduced proteinuria, renal pathology scores and serum urea nitrogen levels compared to wildtype mice, despite higher serum anti-dsDNA levels. ERα deficient MRL/lpr female, but not male, mice also had significantly less proteinuria and renal pathology scores with no effect on autoantibody levels. Deficiency of ERβ had no effect on disease in either strain or sex. Taken together, these data demonstrate a key role for ERα, but not ERβ, in the development of lupus like disease, but not autoimmunity, in female NZM and MRL/lpr mice.

Original language	English (US)
Pages (from-to)	259-268
Number of pages	10
Journal	Clinical Immunology
Volume	128
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2008.03.508
State	Published - Aug 2008

Keywords

Autoimmunity
Estrogen receptors
Lupus
Renal disease

ASJC Scopus subject areas

Immunology
Immunology and Allergy

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@article{db58adfa0ca24503bc7380475240e757,

title = "Impact of estrogen receptor deficiency on disease expression in the NZM2410 lupus prone mouse",

abstract = "Systemic lupus erythematosus (SLE) occurs nine times more often in females than males. The purpose of this study was to determine the impact of estrogen receptor (ER) null genotypes on disease in lupus prone NZM2410 (NZM) and MRL/lpr mice, as a method to define the role of estrogen receptor signaling in lupus. ERα deficient NZM females, but not males, had significantly prolonged survival, reduced proteinuria, renal pathology scores and serum urea nitrogen levels compared to wildtype mice, despite higher serum anti-dsDNA levels. ERα deficient MRL/lpr female, but not male, mice also had significantly less proteinuria and renal pathology scores with no effect on autoantibody levels. Deficiency of ERβ had no effect on disease in either strain or sex. Taken together, these data demonstrate a key role for ERα, but not ERβ, in the development of lupus like disease, but not autoimmunity, in female NZM and MRL/lpr mice.",

keywords = "Autoimmunity, Estrogen receptors, Lupus, Renal disease",

author = "Svenson, {John L.} and Jackie EuDaly and Phil Ruiz and Korach, {Kenneth S.} and Gilkeson, {Gary S.}",

note = "Funding Information: This work was supported by the Medical Research Service, Ralph H. Johnson VAMC and a REAP award from the VA Medical Research Service. The authors are indebted to Drs. John Couse and Derek Henley, NIEHS, for their expertise in estrogen receptor biology.",

year = "2008",

month = aug,

doi = "10.1016/j.clim.2008.03.508",

language = "English (US)",

volume = "128",

pages = "259--268",

journal = "Clinical Immunology",

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AU - EuDaly, Jackie

AU - Ruiz, Phil

AU - Korach, Kenneth S.

AU - Gilkeson, Gary S.

N1 - Funding Information: This work was supported by the Medical Research Service, Ralph H. Johnson VAMC and a REAP award from the VA Medical Research Service. The authors are indebted to Drs. John Couse and Derek Henley, NIEHS, for their expertise in estrogen receptor biology.

PY - 2008/8

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N2 - Systemic lupus erythematosus (SLE) occurs nine times more often in females than males. The purpose of this study was to determine the impact of estrogen receptor (ER) null genotypes on disease in lupus prone NZM2410 (NZM) and MRL/lpr mice, as a method to define the role of estrogen receptor signaling in lupus. ERα deficient NZM females, but not males, had significantly prolonged survival, reduced proteinuria, renal pathology scores and serum urea nitrogen levels compared to wildtype mice, despite higher serum anti-dsDNA levels. ERα deficient MRL/lpr female, but not male, mice also had significantly less proteinuria and renal pathology scores with no effect on autoantibody levels. Deficiency of ERβ had no effect on disease in either strain or sex. Taken together, these data demonstrate a key role for ERα, but not ERβ, in the development of lupus like disease, but not autoimmunity, in female NZM and MRL/lpr mice.

AB - Systemic lupus erythematosus (SLE) occurs nine times more often in females than males. The purpose of this study was to determine the impact of estrogen receptor (ER) null genotypes on disease in lupus prone NZM2410 (NZM) and MRL/lpr mice, as a method to define the role of estrogen receptor signaling in lupus. ERα deficient NZM females, but not males, had significantly prolonged survival, reduced proteinuria, renal pathology scores and serum urea nitrogen levels compared to wildtype mice, despite higher serum anti-dsDNA levels. ERα deficient MRL/lpr female, but not male, mice also had significantly less proteinuria and renal pathology scores with no effect on autoantibody levels. Deficiency of ERβ had no effect on disease in either strain or sex. Taken together, these data demonstrate a key role for ERα, but not ERβ, in the development of lupus like disease, but not autoimmunity, in female NZM and MRL/lpr mice.

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