Integration and expression of a metallothionein-human somatotropin-releasing factor cDNA fusion gene in transgenic mice

In an attempt to use mouse metallothionein-I (mMT-I) regulatory sequences to direct expression of human ornithine transcarbamylase in the liver of transgenic animals, fusion genes joining either 1.6 kilobases or 185 base pairs of the mMT-I regulatory region to the human ornithine transcarbamylase protein-coding sequence were used to produce transgenic mice. In mice carrying the fusion gene with 1.6 kilobases of the mMT-I 5'-flanking sequences, transgene expression was observed in a wide range of tissues, but, unexpectedly, expression in liver was never observed. Surprisingly, in mice carrying the fusion gene regulated by only 185 base pairs of the mMT-I 5'-flanking sequences, the transgene was expressed exclusively in male germ cells during the tetraploid, pachytene stage of meiosis.

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Expression of Human Tyrosine Hydroxylase-Chloramphenicol Acetyltransferase (CAT) Fusion Gene in the Brains of Transgenic Mice as Examined by CAT Immunocytochemistry

Alzheimer’s and Parkinson’s Diseases - Advances in Behavioral Biology ◽

10.1007/978-1-4757-9145-7_98 ◽

1995 ◽

pp. 685-692

Author(s):

Ikuko Nagatsu ◽

Nobuyuki Karasawa ◽

Keiki Yamada ◽

Masao Sakai ◽

Tetsuya Fujii ◽

...

Keyword(s):

Tyrosine Hydroxylase ◽

Transgenic Mice ◽

Fusion Gene ◽

Chloramphenicol Acetyltransferase

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Upstream G gamma-globin and downstream beta-globin sequences required for stage-specific expression in transgenic mice

Molecular and Cellular Biology ◽

10.1128/mcb.7.11.4024-4029.1987 ◽

1987 ◽

Vol 7 (11) ◽

pp. 4024-4029

Author(s):

M Trudel ◽

J Magram ◽

L Bruckner ◽

F Costantini

Keyword(s):

Transgenic Mice ◽

Fusion Gene ◽

Globin Gene ◽

Regulatory Elements ◽

Globin Genes ◽

Beta Globin ◽

Erythroid Cells ◽

Base Pairs ◽

Beta Globin Gene ◽

Gamma Globin

The human G gamma-globin and beta-globin genes are expressed in erythroid cells at different stages of human development, and previous studies have shown that the two cloned genes are also expressed in a differential stage-specific manner in transgenic mice. The G gamma-globin gene is expressed only in murine embryonic erythroid cells, while the beta-globin gene is active only at the fetal and adult stages. In this study, we analyzed transgenic mice carrying a series of hybrid genes in which different upstream, intragenic, or downstream sequences were contributed by the beta-globin or G gamma-globin gene. We found that hybrid 5'G gamma/3'beta globin genes containing G gamma-globin sequences upstream from the initiation codon were expressed in embryonic erythroid cells at levels similar to those of an intact G gamma-globin transgene. In contrast, beta-globin upstream sequences were insufficient for expression of 5'beta/3'G gamma hybrid globin genes or a beta-globin-metallothionein fusion gene in adult erythroid cells. However, beta-globin downstream sequences, including 212 base pairs of exon III and 1,900 base pairs of 3'-flanking DNA, were able to activate a 5'G gamma/3'beta hybrid globin gene in fetal and adult erythroid cells. These experiments suggest that positive regulatory elements upstream from the G gamma-globin and downstream from the beta-globin gene are involved in the differential expression of the two genes during development.

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Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice

Molecular and Cellular Biology ◽

10.1128/mcb.9.12.5473-5479.1989 ◽

1989 ◽

Vol 9 (12) ◽

pp. 5473-5479

Author(s):

C M Shanahan ◽

N W Rigby ◽

J D Murray ◽

J T Marshall ◽

C A Townrow ◽

...

Keyword(s):

Growth Hormone ◽

Transgenic Mice ◽

Mrna Expression ◽

Transgene Expression ◽

Fusion Gene ◽

Developmental Expression ◽

Regulation Of Expression ◽

Tissue Specific ◽

Transgenic Livestock ◽

Main Regulator

Transgenic mice containing a sheep metallothionein 1a-sheep growth hormone fusion gene exhibited low, tissue-specific basal levels of transgene mRNA expression, resulting in slightly elevated levels of circulating growth hormone that did not lead to a detectable increase in growth. After zinc stimulation, high levels of transgene mRNA expression were induced in a number of tissues; these levels correlated with increased levels of circulating growth hormone, resulting in growth increases of up to 1.5 times the levels of controls and unstimulated transgenic mice. After removal of the zinc stimulus, transgene expression and circulating growth hormone concentrations returned to basal levels. Additional evidence from the pattern of developmental expression of the transgene suggests that zinc is the main regulator of this promoter in mice. The demonstrated regulation and low basal level of expression of the sheep metallothionein 1a promoter make it a candidate for use in other mouse transgenic studies and for use in transgenic livestock, in which regulation of expression is essential.

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