Disruption of mouse XAB2 gene involved in pre-mRNA splicing, transcription and transcription-coupled DNA repair results in preimplantation lethality

Rie Yonemasu, Mitsuyoshi Minami, Yoshimichi Nakatsu, Masayo Takeuchi, Isao Kuraoka, Yoichi Matsuda, Yujiro Higashi, Hisato Kondoh, Kiyoji Tanaka

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The XAB2 protein (XPA-binding protein 2) with 15 tetratricopeptide repeat motifs has been isolated by virtue of its ability to interact with xeroderma pigmentosum group A (XPA) protein in the yeast two-hybrid system. It has been shown that XAB2 interacted with Cockayne syndrome groups A and B (CSA and CSB) proteins and RNA polymerase II, which are known to be involved in transcription-coupled repair (TCR) and transcription, and that the antibodies against XAB2 protein inhibited the recovery of RNA synthesis after UV irradiation and normal RNA synthesis when microinjected into living fibroblasts. These results have indicated that XAB2 is involved in TCR and transcription. In this report, to elucidate the function of XAB2 in vivo, two types of mutations were introduced into the XAB2 gene in mice: a deletion of the region encompassing the promoter and exons 1-4, and a deletion of the C-terminal 162 amino acids. Both types of XAB2-heterozygous mice appeared normal physiologically and behaviorally. However, XAB2-homozygotes were selectively absent among the newborn mice. A detailed analysis of embryos at different stages of development indicated that the XAB2-homozygous mutants could survive until the morula stage, but could not develop to the blastocyst stage. These results indicate that XAB2 has an essential function in mouse embryogenesis.

Original languageEnglish
Pages (from-to)479-491
Number of pages13
JournalDNA Repair
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 4 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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