Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor beta-chain: Implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells

被引:44
作者
Nicola, NA
Robb, L
Metcalf, D
Cary, D
Drinkwater, CC
Begley, CG
机构
[1] ROYAL MELBOURNE HOSP, ROTARY BONE MARROW RES LABS, MELBOURNE, VIC 3050, AUSTRALIA
[2] ROYAL MELBOURNE HOSP, WALTER & ELIZA HALL INST MED RES, MELBOURNE, VIC 3050, AUSTRALIA
关键词
D O I
10.1182/blood.V87.7.2665.bloodjournal8772665
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 and -5 (IL-3, IL-5) share a common signaling subunit (beta c). However, in the mouse, IL-3 can also use an alternative IL-3-specific receptor beta-chain (beta IL-3). To assess the relative contributions of beta c and beta IL-3 to IL-3 receptor formation and function, mice were generated in which the beta IL-3 gene was functionally inactivated by replacement of exons 9-13 with a neomycin resistance cassette. Bone marrow cells from these mice displayed a lower affinity IL-3 receptor than normal and were hyporesponsive to IL-3, but the mice displayed no obvious hematopoietic abnormalities. The data suggested that beta c and beta IL-3 are normally coexpressed on IL-3-responsive cells and have identical qualitative signaling capacities. Receptor transmodulation studies on bone marrow cells from wild-type, beta c-/-, and beta IL-3-/- mice showed that the previously described hierarchical pattern of transmodulation was dependent on the relative numbers of both beta IL-3 and beta c receptor chains and also provided evidence for an unexpected interaction between beta c chains and G-CSF and M-CSF receptors. (C) 1996 by The American Society of Hematology.
引用
收藏
页码:2665 / 2674
页数:10
相关论文
共 40 条
[31]  
OGOROCHI T, 1992, BLOOD, V79, P895
[32]   ABSENCE OF YOLK-SAC HEMATOPOIESIS FROM MICE WITH A TARGETED DISRUPTION OF THE SCL GENE [J].
ROBB, L ;
LYONS, I ;
LI, RL ;
HARTLEY, L ;
KONTGEN, F ;
HARVEY, RP ;
METCALF, D ;
BEGLEY, CG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (15) :7075-7079
[33]   HEMATOPOIETIC AND LUNG ABNORMALITIES IN MICE WITH A NULL MUTATION OF THE COMMON BETA-SUBUNIT OF THE RECEPTORS FOR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-3 AND INTERLEUKIN-5 [J].
ROBB, L ;
DRINKWATER, CC ;
METCALF, D ;
LI, RL ;
KONTGEN, F ;
NICOLA, NA ;
BEGLEY, CG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (21) :9565-9569
[34]  
ROHRSCHNEIDER LR, 1989, ONCOGENE, V4, P1015
[35]   MAC-1 - MACROPHAGE DIFFERENTIATION ANTIGEN IDENTIFIED BY MONOCLONAL ANTIBODY [J].
SPRINGER, T ;
GALFRE, G ;
SECHER, DS ;
MILSTEIN, C .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1979, 9 (04) :301-306
[36]   BCL-2 TRANSGENE INHIBITS T-CELL DEATH AND PERTURBS THYMIC SELF-CENSORSHIP [J].
STRASSER, A ;
HARRIS, AW ;
CORY, S .
CELL, 1991, 67 (05) :889-899
[37]  
SZABO P, 1994, DEVELOPMENT, V120, P1651
[38]   A HUMAN HIGH-AFFINITY INTERLEUKIN-5 RECEPTOR (IL5R) IS COMPOSED OF AN IL5-SPECIFIC ALPHA-CHAIN AND A BETA-CHAIN SHARED WITH THE RECEPTOR FOR GM-CSF [J].
TAVERNIER, J ;
DEVOS, R ;
CORNELIS, S ;
TUYPENS, T ;
VANDERHEYDEN, J ;
FIERS, W ;
PLAETINCK, G .
CELL, 1991, 66 (06) :1175-1184
[39]   NEONATAL LETHALITY AND LYMPHOPENIA IN MICE WITH A HOMOZYGOUS DISRUPTION OF THE C-ABL PROTOONCOGENE [J].
TYBULEWICZ, VLJ ;
CRAWFORD, CE ;
JACKSON, PK ;
BRONSON, RT ;
MULLIGAN, RC .
CELL, 1991, 65 (07) :1153-1163
[40]   HIERARCHICAL DOWN-MODULATION OF HEMATOPOIETIC GROWTH-FACTOR RECEPTORS [J].
WALKER, F ;
NICOLA, NA ;
METCALF, D ;
BURGESS, AW .
CELL, 1985, 43 (01) :269-276