Reduced expression of the endothelin receptor type B gene in piebald mice caused by insertion of a retroposon-like element in intron 1

Takahisa Yamada, Shin Ohtani, Takeshi Sakurai, Takehito Tsuji, Tetsuo Kunieda, Masashi Yanagisawa

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Mice carrying the piebald mutation exhibit white coat spotting due to the regional absence of neural crest-derived melanocytes. We reported previously that the piebald locus encodes the Ednrb gene and that piebald mice express low levels of structurally intact Ednrb mRNA and EDNRB protein (Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., and Yanagisawa, M. (1994) Cell 79, 1267-1276). Here, we report that both the life span of the Ednrb mRNA and the promoter activity of the Ednrb gene are indistinguishable between wild-type and piebald mice. Introns 2-6 of the Ednrb gene in piebald mice were correctly excised with an efficiency indistinguishable from those in wild-type mice in exon trapping experiments.Wefound that the piebald allele of the Ednrb gene has a 5.5-kb retroposon-like element in intron 1 possessing canonical sequences of a polyadenylation signal and a splice acceptor site. Abnormal hybrid transcripts carrying exon 1 of the Ednrb gene and a portion of the 5.5-kb element are expressed in piebald mice. The insertion of the 5.5-kb element into a heterologous intron in a mammalian expression vector markedly reduced the expression of the reporter gene. Premature termination and aberrant splicing of the Ednrb transcript caused by the retroposon-like element in intron 1 lead to a reduced level of the normal Ednrb transcript, which is responsible for the partial loss-of-function phenotype of piebald mice.

Original languageEnglish (US)
Pages (from-to)10799-10807
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number16
DOIs
StatePublished - Apr 21 2006

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Endothelin B Receptors
Retroelements
Introns
Genes
Exons
Messenger RNA
RNA Splice Sites
Metrorrhagia
Polyadenylation
Neural Crest
Melanocytes
Reporter Genes
Alleles
Phenotype
Mutation

ASJC Scopus subject areas

  • Biochemistry

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Reduced expression of the endothelin receptor type B gene in piebald mice caused by insertion of a retroposon-like element in intron 1. / Yamada, Takahisa; Ohtani, Shin; Sakurai, Takeshi; Tsuji, Takehito; Kunieda, Tetsuo; Yanagisawa, Masashi.

In: Journal of Biological Chemistry, Vol. 281, No. 16, 21.04.2006, p. 10799-10807.

Research output: Contribution to journalArticle

Yamada, Takahisa ; Ohtani, Shin ; Sakurai, Takeshi ; Tsuji, Takehito ; Kunieda, Tetsuo ; Yanagisawa, Masashi. / Reduced expression of the endothelin receptor type B gene in piebald mice caused by insertion of a retroposon-like element in intron 1. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 16. pp. 10799-10807.
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abstract = "Mice carrying the piebald mutation exhibit white coat spotting due to the regional absence of neural crest-derived melanocytes. We reported previously that the piebald locus encodes the Ednrb gene and that piebald mice express low levels of structurally intact Ednrb mRNA and EDNRB protein (Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., and Yanagisawa, M. (1994) Cell 79, 1267-1276). Here, we report that both the life span of the Ednrb mRNA and the promoter activity of the Ednrb gene are indistinguishable between wild-type and piebald mice. Introns 2-6 of the Ednrb gene in piebald mice were correctly excised with an efficiency indistinguishable from those in wild-type mice in exon trapping experiments.Wefound that the piebald allele of the Ednrb gene has a 5.5-kb retroposon-like element in intron 1 possessing canonical sequences of a polyadenylation signal and a splice acceptor site. Abnormal hybrid transcripts carrying exon 1 of the Ednrb gene and a portion of the 5.5-kb element are expressed in piebald mice. The insertion of the 5.5-kb element into a heterologous intron in a mammalian expression vector markedly reduced the expression of the reporter gene. Premature termination and aberrant splicing of the Ednrb transcript caused by the retroposon-like element in intron 1 lead to a reduced level of the normal Ednrb transcript, which is responsible for the partial loss-of-function phenotype of piebald mice.",
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