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PMID: 2119506 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Immune deficiency due to high copy numbers of an Ak beta transgene.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 18 ·1990-09-00 ·Pages 7319-23

Gilfillan S, Aiso S, Michie SA, McDevitt HO

Abstract

Because allelic polymorphism of the major histocompatibility complex class II antigens affects the immune response at several levels, we wished to characterize the contribution of a particular alpha or beta chain in vivo using transgenic mice. We have established and characterized 12 lines of H-2s/s mice carrying from 1 to 65 copies of an Ak beta transgene. The transgene was coexpressed with the endogenous allele in a tissue-specific manner, and Ak beta mRNA expression correlated well with transgene copy number. High copy number (extreme overexpression) of the transgene was associated with a variety of defects, including a significant reduction in Ia cell-surface expression, a severe decrease in B-cell number, abnormal extramedullary granulopoiesis, and an increased susceptibility to infection. In this paper we describe in detail the phenotype associated with high copy numbers of the Ak beta transgene. The defects we have observed may be relevant to similar phenomena seen in other transgenic mice. In addition, these mice have fortuitously provided a system in which to assess the effect of various levels of class II cell-surface expression in the thymus on selection of the T-cell repertoire.

MeSH Terms
Alleles Animals Antibodies, Monoclonal B-Lymphocytes/immunology Female Flow Cytometry Gene Expression Genes, MHC Class II Histocompatibility Antigens Class II/genetics Immunohistochemistry Immunologic Deficiency Syndromes/genetics Lymphocyte Depletion Male Mice Mice, Inbred Strains Mice, Transgenic Polymorphism, Genetic RNA, Messenger/genetics Spleen/immunology
Chemicals
Antibodies, Monoclonal Histocompatibility Antigens Class II RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gilfillan S
Department of Microbiology and Immunology, Stanford School of Medicine, CA 94305.
Aiso S
Michie S A
McDevitt H O
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.18.7319
Published
1990-09-00
Pages
7319-23
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54735
Subset
IM
Grants
NCI NIH HHS · 5T32 CA 09302 · United States
NIAID NIH HHS · AI19512 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.18.7319 PMC Full Text View journal details
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