Expression of a TNF inhibitorin transgenic mice

K. Peppel, A. Poltorak, I. Melhado, F. Jirik, B. Beutler

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

We previously reported that a chimeric protein consisting of the human p55 TNF receptor covalently linked to a murine IgG1 Fc heavy chain acts as an efficient TNF inhibitor, as a result of its high binding affinity for native TNF trimers of both murine and human origin. A transgenic mouse line constitutively expressing the inhibitor from a cytomegalovirus promoter was established. All organs examined expressed the transgene. TNF inhibitory activity was easily detected in plasma of transgenic animals but not in plasma of nontransgenic littermates. This founder line was not found to have any obvious phenotype. Specifically, transgenic mice born to wild-type or transgenic females were indistinguishable from nontransgenic littermates with respect to their size at birth, at three months and at six months of age, with respect to the size and morphology of their lymphoid organs and with respect to their hematocrit, white blood cell count, and differential. Although TNF is known to be constitutively expressed by cells of the thymus and trophoblast, the lack of a clear phenotype in association with the constitutive expression of a TNF inhibitor suggests that TNF may be dispensable in early development.

Original languageEnglish (US)
Pages (from-to)5699-5703
Number of pages5
JournalJournal of Immunology
Volume151
Issue number10
StatePublished - Nov 15 1993

Fingerprint

Transgenic Mice
Phenotype
Genetically Modified Animals
Trophoblasts
Cytomegalovirus
Transgenes
Leukocyte Count
Hematocrit
Thymus Gland
Immunoglobulin G
Parturition
Proteins
recombinant human tumor necrosis factor-binding protein-1

ASJC Scopus subject areas

  • Immunology

Cite this

Peppel, K., Poltorak, A., Melhado, I., Jirik, F., & Beutler, B. (1993). Expression of a TNF inhibitorin transgenic mice. Journal of Immunology, 151(10), 5699-5703.

Expression of a TNF inhibitorin transgenic mice. / Peppel, K.; Poltorak, A.; Melhado, I.; Jirik, F.; Beutler, B.

In: Journal of Immunology, Vol. 151, No. 10, 15.11.1993, p. 5699-5703.

Research output: Contribution to journalArticle

Peppel, K, Poltorak, A, Melhado, I, Jirik, F & Beutler, B 1993, 'Expression of a TNF inhibitorin transgenic mice', Journal of Immunology, vol. 151, no. 10, pp. 5699-5703.
Peppel K, Poltorak A, Melhado I, Jirik F, Beutler B. Expression of a TNF inhibitorin transgenic mice. Journal of Immunology. 1993 Nov 15;151(10):5699-5703.
Peppel, K. ; Poltorak, A. ; Melhado, I. ; Jirik, F. ; Beutler, B. / Expression of a TNF inhibitorin transgenic mice. In: Journal of Immunology. 1993 ; Vol. 151, No. 10. pp. 5699-5703.
@article{4d4b2655b699442e91ca3e86fb903d43,
title = "Expression of a TNF inhibitorin transgenic mice",
abstract = "We previously reported that a chimeric protein consisting of the human p55 TNF receptor covalently linked to a murine IgG1 Fc heavy chain acts as an efficient TNF inhibitor, as a result of its high binding affinity for native TNF trimers of both murine and human origin. A transgenic mouse line constitutively expressing the inhibitor from a cytomegalovirus promoter was established. All organs examined expressed the transgene. TNF inhibitory activity was easily detected in plasma of transgenic animals but not in plasma of nontransgenic littermates. This founder line was not found to have any obvious phenotype. Specifically, transgenic mice born to wild-type or transgenic females were indistinguishable from nontransgenic littermates with respect to their size at birth, at three months and at six months of age, with respect to the size and morphology of their lymphoid organs and with respect to their hematocrit, white blood cell count, and differential. Although TNF is known to be constitutively expressed by cells of the thymus and trophoblast, the lack of a clear phenotype in association with the constitutive expression of a TNF inhibitor suggests that TNF may be dispensable in early development.",
author = "K. Peppel and A. Poltorak and I. Melhado and F. Jirik and B. Beutler",
year = "1993",
month = "11",
day = "15",
language = "English (US)",
volume = "151",
pages = "5699--5703",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Expression of a TNF inhibitorin transgenic mice

AU - Peppel, K.

AU - Poltorak, A.

AU - Melhado, I.

AU - Jirik, F.

AU - Beutler, B.

PY - 1993/11/15

Y1 - 1993/11/15

N2 - We previously reported that a chimeric protein consisting of the human p55 TNF receptor covalently linked to a murine IgG1 Fc heavy chain acts as an efficient TNF inhibitor, as a result of its high binding affinity for native TNF trimers of both murine and human origin. A transgenic mouse line constitutively expressing the inhibitor from a cytomegalovirus promoter was established. All organs examined expressed the transgene. TNF inhibitory activity was easily detected in plasma of transgenic animals but not in plasma of nontransgenic littermates. This founder line was not found to have any obvious phenotype. Specifically, transgenic mice born to wild-type or transgenic females were indistinguishable from nontransgenic littermates with respect to their size at birth, at three months and at six months of age, with respect to the size and morphology of their lymphoid organs and with respect to their hematocrit, white blood cell count, and differential. Although TNF is known to be constitutively expressed by cells of the thymus and trophoblast, the lack of a clear phenotype in association with the constitutive expression of a TNF inhibitor suggests that TNF may be dispensable in early development.

AB - We previously reported that a chimeric protein consisting of the human p55 TNF receptor covalently linked to a murine IgG1 Fc heavy chain acts as an efficient TNF inhibitor, as a result of its high binding affinity for native TNF trimers of both murine and human origin. A transgenic mouse line constitutively expressing the inhibitor from a cytomegalovirus promoter was established. All organs examined expressed the transgene. TNF inhibitory activity was easily detected in plasma of transgenic animals but not in plasma of nontransgenic littermates. This founder line was not found to have any obvious phenotype. Specifically, transgenic mice born to wild-type or transgenic females were indistinguishable from nontransgenic littermates with respect to their size at birth, at three months and at six months of age, with respect to the size and morphology of their lymphoid organs and with respect to their hematocrit, white blood cell count, and differential. Although TNF is known to be constitutively expressed by cells of the thymus and trophoblast, the lack of a clear phenotype in association with the constitutive expression of a TNF inhibitor suggests that TNF may be dispensable in early development.

UR - http://www.scopus.com/inward/record.url?scp=0027333435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027333435&partnerID=8YFLogxK

M3 - Article

VL - 151

SP - 5699

EP - 5703

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -