A 6-kb upstream region of the human transthyretin gene can direct developmental, tissue-specific, and quantitatively normal expression in transgenic mouse.
To ascertain whether a 6-kb upstream region of the human transthyretin (TTR) gene contains the cis-element(s) required for proper specificity and level of expression, transgenic mice carrying the human mutant TTR gene containing either 6-kb (6.0-hMet30) or 0.6-kb (0.6-hMet30) of the upstream region were produced and studied. The 6.0-hMet30 gene was expressed in the yolk sac, liver, and choroid plexus, where the mouse endogenous TTR gene is also expressed. In contrast, expression of the 0.6-hMet30 gene was restricted to the yolk sac and liver. The expression levels of the 6.0-hMet30 gene in the liver and serum were similar to those of the mouse TTR gene, and about 10-fold those of the 0.6-hMet30 gene. Before birth, the developmental profiles of the expression of both transgenes in each tissue were similar to those of the mouse TTR gene. However, the expression levels of the 6.0-hMet30 gene in the liver and serum increased after birth to reach adult levels at an age of 4 weeks, while expression of the 0.6-hMet30 gene remained at a low level after birth. These results suggest that the 6-kb upstream sequence contains the cis-elements required for developmental, tissue-specific, and quantitatively normal expression.
Nagata
Y
Y
Department of Obstetrics and Gynecology, Kumamoto University School of Medicine.
Tashiro
F
F
Yi
S
S
Murakami
T
T
Maeda
S
S
Takahashi
K
K
Shimada
K
K
Okamura
H
H
Yamamura
K
K
D000818:Animals; D001482:Base Composition; D001921:Brain / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008715:Methionine / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009841:Oligonucleotides / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics*; D011228:Prealbumin / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values
D009841:Oligonucleotides; D011228:Prealbumin; D012333:RNA, Messenger; D008715:Methionine