Regulated expression of a murine class I gene in transgenic mice

1986 ◽  
Vol 6 (4) ◽  
pp. 1339-1342
Author(s):  
C Bieberich ◽  
G Scangos ◽  
K Tanaka ◽  
G Jay
Keyword(s):  
Transgenic Mice ◽  
Germ Line ◽  
Inbred Mice ◽  
Class I ◽  
Endogenous Gene ◽  
Histocompatibility Complex ◽  
Unique System ◽  
Regulated Expression ◽  
I Gene

The major histocompatibility complex class I genes play an essential role in the immune presentation of aberrant cells. To gain further insight into the regulation of the expression of these class I genes and to better define the functions of their protein products, we made use of the technique of gene transfer into the germ line of inbred mice. With the use of locus-specific DNA probes, we observed that a transgenic class I gene was expressed in a tissue-dependent fashion analogous to that of an endogenous class I gene. In addition, the level of expression of the transgenic gene was substantially higher that that of the endogenous gene. The availability of transgenic mice properly expressing a foreign murine class I gene provides a unique system to further define the role of the class I antigens in the maturation of the immune response and in determining the malignant and metastatic phenotypes of tumor cells.

scholarly journals Regulated expression of a murine class I gene in transgenic mice.

1986 ◽  
Vol 6 (4) ◽  
pp. 1339-1342 ◽  
Author(s):  
C Bieberich ◽  
G Scangos ◽  
K Tanaka ◽  
G Jay
Keyword(s):  
Transgenic Mice ◽  
Germ Line ◽  
Inbred Mice ◽  
Class I ◽  
Endogenous Gene ◽  
Histocompatibility Complex ◽  
Unique System ◽  
Regulated Expression ◽  
I Gene

The major histocompatibility complex class I genes play an essential role in the immune presentation of aberrant cells. To gain further insight into the regulation of the expression of these class I genes and to better define the functions of their protein products, we made use of the technique of gene transfer into the germ line of inbred mice. With the use of locus-specific DNA probes, we observed that a transgenic class I gene was expressed in a tissue-dependent fashion analogous to that of an endogenous class I gene. In addition, the level of expression of the transgenic gene was substantially higher that that of the endogenous gene. The availability of transgenic mice properly expressing a foreign murine class I gene provides a unique system to further define the role of the class I antigens in the maturation of the immune response and in determining the malignant and metastatic phenotypes of tumor cells.

Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice

1987 ◽  
Vol 7 (11) ◽  
pp. 4003-4009
Author(s):  
C Bieberich ◽  
T Yoshioka ◽  
K Tanaka ◽  
G Jay ◽  
G Scangos
Keyword(s):  
Major Histocompatibility Complex ◽  
Transgenic Mice ◽  
Major Histocompatibility Complex Class ◽  
Inbred Mice ◽  
Class I ◽  
Dependent Manner ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
I Gene

The regulated expression of major histocompatibility complex class I antigens is essential for assuring proper cellular immune responses. To study H-2 class I gene regulation, we have transferred a foreign class I gene to inbred mice and have previously shown that the heterologous class I gene was expressed in a tissue-dependent manner. In this report, we demonstrate that these mice expressed the transgenic class I molecule on the cell surface without any alteration in the level of endogenous H-2 class I antigens. Skin grafts from transgenic mice were rapidly rejected by mice of the background strain, indicating that the transgenic antigen was expressed in an immunologically functional form. As with endogenous H-2 class I genes, the class I transgene was inducible by interferon treatment and suppressible by human adenovirus 12 transformation. Linkage analysis indicated that the transgene was not closely linked to endogenous class I loci, suggesting that trans-regulation of class I genes can occur for class I genes located outside the major histocompatibility complex.

scholarly journals Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice.

1987 ◽  
Vol 7 (11) ◽  
pp. 4003-4009 ◽  
Author(s):  
C Bieberich ◽  
T Yoshioka ◽  
K Tanaka ◽  
G Jay ◽  
G Scangos
Keyword(s):  
Major Histocompatibility Complex ◽  
Transgenic Mice ◽  
Major Histocompatibility Complex Class ◽  
Inbred Mice ◽  
Class I ◽  
Dependent Manner ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
I Gene

The regulated expression of major histocompatibility complex class I antigens is essential for assuring proper cellular immune responses. To study H-2 class I gene regulation, we have transferred a foreign class I gene to inbred mice and have previously shown that the heterologous class I gene was expressed in a tissue-dependent manner. In this report, we demonstrate that these mice expressed the transgenic class I molecule on the cell surface without any alteration in the level of endogenous H-2 class I antigens. Skin grafts from transgenic mice were rapidly rejected by mice of the background strain, indicating that the transgenic antigen was expressed in an immunologically functional form. As with endogenous H-2 class I genes, the class I transgene was inducible by interferon treatment and suppressible by human adenovirus 12 transformation. Linkage analysis indicated that the transgene was not closely linked to endogenous class I loci, suggesting that trans-regulation of class I genes can occur for class I genes located outside the major histocompatibility complex.

scholarly journals Gene conversion in the evolution of both the H-2 and Qa class I genes of the murine major histocompatibility complex.

Genetics ◽  
1990 ◽  
Vol 126 (4) ◽  
pp. 1115-1126
Author(s):  
M Kuhner ◽  
S Watts ◽  
W Klitz ◽  
G Thomson ◽  
R S Goodenow
Keyword(s):  
Major Histocompatibility Complex ◽  
Gene Conversion ◽  
Dna Sequences ◽  
Class I ◽  
Major Histocompatibility ◽  
Gene Encoding ◽  
Histocompatibility Complex ◽  
Sequence Similarities ◽  
I Gene

Abstract In order to better understand the role of gene conversion in the evolution of the class I gene family of the major histocompatibility complex (MHC), we have used a computer algorithm to detect clustered sequence similarities among 24 class I DNA sequences from the H-2, Qa, and Tla regions of the murine MHC. Thirty-four statistically significant clusters were detected; individual analysis of the clusters suggested at least 25 past gene conversion or recombination events. These clusters are comparable in size to the conversions observed in the spontaneously occurring H-2Kbm and H-2Kkm2 mutations, and are distributed throughout all exons of the class I gene. Thus, gene conversion does not appear to be restricted to the regions of the class I gene encoding their antigen-presentation function. Moreover, both the highly polymorphic H-2 loci and the relatively monomorphic Qa and Tla loci appear to have participated as donors and recipients in conversion events. If gene conversion is not limited to the highly polymorphic loci of the MHC, then another factor, presumably natural selection, must be responsible for maintaining the observed differences in level of variation.

scholarly journals A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes.

1990 ◽  
Vol 10 (8) ◽  
pp. 4100-4109 ◽  
Author(s):  
U Henseling ◽  
W Schmidt ◽  
H R Schöler ◽  
P Gruss ◽  
A K Hatzopoulos
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cell Lines ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mouse Tissues ◽  
I Gene

AKR leukemias display different amounts of major histocompatibility complex class I antigens on the cell surface. The absence of H-2Kk molecules correlates with the ability of these cell lines to form tumors in vivo as well as to escape lysis by cytotoxic T lymphocytes in vitro. In this report it is shown that the 5' regulatory area of the H-2Kk gene failed to activate transcription in H-2Kk-negative cells. Examination of the proteins interacting with the H-2Kk enhancer in expressing and nonexpressing cells revealed clear differences. In particular, the level of a nuclear protein interacting at position -166 was greatly reduced in the negative cell lines. A transcription factor, known as H2TF1 or KBF1, has been shown previously to interact with this binding site and to be essential for the expression of certain class I genes as well as the expression of beta 2-microglobulin. These results demonstrate that the molecular mechanism of class I gene suppression in malignant tumor cells is at the level of transcription and is most probably modulated by H2TF1/KBFI. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens.

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