Indispensable function for embryogenesis, expression and regulation of the nonspecific form of the 5-aminolevulinate synthase gene in mouse

Satoshi Okano, Lingyun Zhou, Toshimasa Kusaka, Kazuhide Shibata, Kazuhiro Shimizu, Xu Gao, Yuko Kikuchi, Yoshiyuki Togashi, Tomonori Hosoya, Satoru Takahashi, Osamu Nakajima, Masayuki Yamamoto

研究成果: Article査読

19 被引用数 (Scopus)

抄録

The first step of heme biosynthesis in animals is catalyzed by 5-aminolevulinate synthase (ALAS), which controls heme supply in various tissues. To clarify the roles that the nonspecific isoform of ALAS (ALAS-N) plays in vivo, we prepared a green fluorescent protein (GFP) knock-in mouse line in which the Alas1 gene (encoding ALAS-N) is replaced with a gfp gene. We found that mice bearing a homozygous knock-in allele (Alas1GFP/GFP) were lethal by embryonic day 8.5, demonstrating that ALAS-N is essential for early embryogenesis. Fluorescence microscopic and flow cytometric analyses of heterozygous mouse (Alas1+/GFP) tissues showed that the Alas1 expression level differs substantially in tissues; Alas1 is highly expressed in testis Leydig cells, exocrine glands (including submandibular and parotid glands), endocrine glands (such as adrenal and thyroid glands) and hematopoietic lineage cells (including neutrophils and eosinophils). Quantitative analyses of GFP mRNA and ALAS-N mRNA in various tissues of Alas1+/GFP mice suggested that the destabilization of ALAS-N mRNA was not uniform in the various tissues. These results thus lay bare that elaborate control of the endogenous heme supply operates in various mouse tissues through regulation of the ALAS-N expression level and that this control is essential for heme homeostasis in animals.

本文言語English
ページ(範囲)77-89
ページ数13
ジャーナルGenes to Cells
15
1
DOI
出版ステータスPublished - 2010 1月

ASJC Scopus subject areas

  • 遺伝学
  • 細胞生物学

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