Targeted disruption of the mouse STAT1 results in compromised innate immunity to viral disease

被引：1300

作者：

Durbin, JE

Hackenmiller, R

Simon, MC

Levy, DE

机构：

[1] NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016

[2] NYU,SCH MED,KAPLAN CANC CTR,NEW YORK,NY 10016

[3] UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637

[4] UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637

来源：

CELL | 1996年 / 84卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S0092-8674(00)81289-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The STAT1 transcription factor is activated in response to many cytokines and growth factors. To study the requirement for STAT1 in vivo, we disrupted the Stat1 gene in embryonic stem (ES) cells and in mice. Stat1(-/-) ES cells were unresponsive to interferon (IFN), but retained responsiveness to leukemia inhibitory factor (LIF) and remained LIF dependent for undifferentiated growth. Stat1(-/-) animals were born at normal frequencies and displayed no gross developmental defects. However, these animals failed to thrive and were extremely susceptible to viral disease. Cells and tissues from Stat1(-/-) mice were unresponsive to IFN, but remained responsive to all other cytokines tested. Thus, STAT1 appears to be specific for IFN pathways that are essential for viability in the face of otherwise innocuous pathogens.

引用

页码：443 / 450

页数：8

共 62 条

[1] BHAT GJ, 1994, J BIOL CHEM, V269, P31443
[2] COMBINATORIAL ASSOCIATION AND ABUNDANCE OF COMPONENTS OF INTERFERON-STIMULATED GENE FACTOR-3 DICTATE THE SELECTIVITY OF INTERFERON RESPONSES
BLUYSSEN, HAR
MUZAFFAR, R
VLIESTSTRA, RJ
VANDERMADE, ACJ
LEUNG, S
STARK, GR
KERR, IM
TRAPMAN, J
LEVY, DE
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) : 5645 - 5649
[3] STAT3 ACTIVATION BY CYTOKINES UTILIZING GP130 AND RELATED TRANSDUCERS INVOLVES A SECONDARY MODIFICATION REQUIRING AN H7-SENSITIVE KINASE
BOULTON, TG
ZHONG, Z
WEN, ZL
DARNELL, JE
STAHL, N
YANCOPOULOS, GD
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (15) : 6915 - 6919
[4] FORMATION OF GERM-LINE CHIMERAS FROM EMBRYO-DERIVED TERATOCARCINOMA CELL-LINES
BRADLEY, A
EVANS, M
KAUFMAN, MH
ROBERTSON, E
[J]. NATURE, 1984, 309 (5965) : 255 - 256
[5] ACTIVATION OF ACUTE-PHASE RESPONSE FACTOR (APRF)/STAT3 TRANSCRIPTION FACTOR BY GROWTH-HORMONE
CAMPBELL, GS
MEYER, DJ
RAZ, R
LEVY, DE
SCHWARTZ, J
CARTERSU, C
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (08) : 3974 - 3979
[6] COMPTON SR, 1993, LAB ANIM SCI, V43, P15
[7] JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS
DARNELL, JE
KERR, IM
STARK, GR
[J]. SCIENCE, 1994, 264 (5164) : 1415 - 1421
[8] PROLACTIN ACTIVATES THE INTERFERON-REGULATED P91 TRANSCRIPTION FACTOR AND THE JAK2 KINASE BY TYROSINE PHOSPHORYLATION
DAVID, M
PETRICOIN, EF
IGARASHI, K
FELDMAN, GM
FINBLOOM, DS
LARNER, AC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (15) : 7174 - 7178
[9] ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI
DIGNAM, JD
LEBOVITZ, RM
ROEDER, RG
[J]. NUCLEIC ACIDS RESEARCH, 1983, 11 (05) : 1475 - 1489
[10] EVIDENCE FOR A NUCLEAR FACTOR(S), IRF-1, MEDIATING INDUCTION AND SILENCING PROPERTIES TO HUMAN IFN-BETA GENE REGULATORY ELEMENTS
FUJITA, T
SAKAKIBARA, J
SUDO, Y
MIYAMOTO, M
KIMURA, Y
TANIGUCHI, T
[J]. EMBO JOURNAL, 1988, 7 (11) : 3397 - 3405

← 1 2 3 4 5 6 7 →