scholarly journals Regulatory region in choline acetyltransferase gene directs developmental and tissue-specific expression in transgenic mice.

1995 ◽  
Vol 92 (9) ◽  
pp. 4046-4050 ◽  
Author(s):  
P. Lonnerberg ◽  
U. Lendahl ◽  
H. Funakoshi ◽  
L. Arhlund-Richter ◽  
H. Persson ◽  
...  

1991 ◽  
Vol 11 (4) ◽  
pp. 2066-2074 ◽  
Author(s):  
J L Slack ◽  
D J Liska ◽  
P Bornstein

Studies in vitro have not adequately resolved the role of intronic and upstream elements in regulating expression of the alpha 1(I) collagen gene. To address this issue, we generated 12 separate lines of transgenic mice with alpha 1(I) collagen-human growth hormone (hGH) constructs containing different amounts of 5'-flanking sequence, with or without most of the first intron. Transgenes driven by 2.3 kb of alpha 1(I) 5'-flanking sequence, whether or not they contained the first intron, were expressed at a high level and in a tissue-specific manner in seven out of seven independent lines of transgenic mice. In most tissues, the transgene was expressed at levels approaching that of the endogenous alpha 1(I) gene and was regulated identically with the endogenous gene as animals aged. However, in lung, expression of the transgene was anomalously high, and in muscle, expression was lower than that of the endogenous gene, suggesting that in these tissues other regions of the gene may participate in directing appropriate expression. Five lines of mice were generated containing transgenes driven by 0.44 kb of alpha 1(I) 5'-flanking sequence (with or without the first intron), and expression was detected in four out of five of these lines. The level of expression of the 0.44-kb constructs in the major collagen-producing tissues was 15- to 500-fold lower than that observed with the longer 2.3-kb promoter. While transgenes containing the 0.44-kb promoter and the first intron retained a modest degree of tissue-specific expression, those without the first intron lacked tissue specificity and were poorly expressed in all tissues except lung.(ABSTRACT TRUNCATED AT 250 WORDS)



1991 ◽  
Vol 11 (4) ◽  
pp. 2066-2074
Author(s):  
J L Slack ◽  
D J Liska ◽  
P Bornstein

Studies in vitro have not adequately resolved the role of intronic and upstream elements in regulating expression of the alpha 1(I) collagen gene. To address this issue, we generated 12 separate lines of transgenic mice with alpha 1(I) collagen-human growth hormone (hGH) constructs containing different amounts of 5'-flanking sequence, with or without most of the first intron. Transgenes driven by 2.3 kb of alpha 1(I) 5'-flanking sequence, whether or not they contained the first intron, were expressed at a high level and in a tissue-specific manner in seven out of seven independent lines of transgenic mice. In most tissues, the transgene was expressed at levels approaching that of the endogenous alpha 1(I) gene and was regulated identically with the endogenous gene as animals aged. However, in lung, expression of the transgene was anomalously high, and in muscle, expression was lower than that of the endogenous gene, suggesting that in these tissues other regions of the gene may participate in directing appropriate expression. Five lines of mice were generated containing transgenes driven by 0.44 kb of alpha 1(I) 5'-flanking sequence (with or without the first intron), and expression was detected in four out of five of these lines. The level of expression of the 0.44-kb constructs in the major collagen-producing tissues was 15- to 500-fold lower than that observed with the longer 2.3-kb promoter. While transgenes containing the 0.44-kb promoter and the first intron retained a modest degree of tissue-specific expression, those without the first intron lacked tissue specificity and were poorly expressed in all tissues except lung.(ABSTRACT TRUNCATED AT 250 WORDS)



1992 ◽  
Vol 20 (9) ◽  
pp. 2249-2255 ◽  
Author(s):  
Thomas R. Mikkelsen ◽  
Jakob Brandt ◽  
H.Jakob Larsen ◽  
Birte B. Larsen ◽  
Knud Poulsen ◽  
...  


Cell ◽  
1984 ◽  
Vol 38 (3) ◽  
pp. 639-646 ◽  
Author(s):  
Galvin H. Swift ◽  
Robert E. Hammer ◽  
Raymond J. MacDonald ◽  
Ralph L. Brinster




1995 ◽  
Vol 4 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Martin Hergersberg ◽  
Koichi Matsuo ◽  
Max Gassmann ◽  
Walter Schaffner ◽  
Bernhard Lüscher ◽  
...  


1989 ◽  
Vol 186 (1-2) ◽  
pp. 43-48 ◽  
Author(s):  
Jean-Luc VILOTTE ◽  
Solange SOULIER ◽  
Marie-George STINNAKRE ◽  
Micheline MASSOUD ◽  
Jean-Claude MERCIER


1988 ◽  
Vol 16 (3) ◽  
pp. 1027-1041 ◽  
Author(s):  
Kuo-Fen Lee ◽  
Francesco J. DeMayo ◽  
Suzanne H. Atiee ◽  
Jeffrey M. Rosen




2004 ◽  
Vol 17 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Ravi Nistala ◽  
Xiaoji Zhang ◽  
Curt D. Sigmund

We previously reported the development and characterization of transgenic mice containing a large 160-kb P1 artificial chromosome (PAC) encompassing the renin (REN) locus from human chromosome 1. Here we demonstrate that PAC160 not only encodes REN, but also complete copies of the next upstream (KISS1) and downstream ( FLJ10761 ) gene along human chromosome 1. Incomplete copies of the second upstream (PEPP3) and downstream (SOX13) genes are also present. The gene order PEPP3-KISS1-REN-FLJ10761-SOX13 is conserved in mice containing either one or two copies of the REN locus. Despite the close localization of KISS1, REN, and FLJ10761 , they each exhibit distinct, yet overlapping tissue-specific expression profiles in humans. The tissue-specific expression patterns of REN and FLJ10761 were retained in transgenic mice containing PAC160. Expression of REN and FLJ10761 were also proportional to copy number. Expression of KISS1 in PAC160 mice showed both similarities and differences to humans. These data suggest that expression of gene blocks encoded on large genomic clones are retained when the clones are used to generate transgenic mice. Genomic elements which act to insulate genes from their neighbors are also apparently retained.



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