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Structure and expression of the mouse growth hormone receptor/growth hormone binding protein gene

J G Moffat1, A Edens, F Talamantes

  • 1Department of Biology, University of California, Santa Cruz, California 95060, USA.

Journal of Molecular Endocrinology
|July 30, 1999
PubMed

Insights

This study details the mouse growth hormone receptor/binding protein (GHR/BP) gene structure, identifying unique exons and regulatory regions. It clarifies alternative splicing and 5' untranslated region (5'UTR) usage, crucial for GHR/BP gene expression. Keywords: mouse GHR/BP gene, alternative splicing, 5'UTR.

Area of Science:

  • Molecular Biology
  • Genetics
  • Gene Expression

Background:

  • The mouse growth hormone receptor/growth hormone-binding protein (GHR/BP) gene exhibits complex alternative splicing, producing distinct mRNA variants.
  • Transcriptional heterogeneity arises from alternative selection of two major 5' untranslated region (5'UTR) sequences, L1 and L2.

Purpose of the Study:

  • To clone and characterize all mouse GHR/BP coding exons and the exon encoding the widely expressed 5'UTR L2.
  • To investigate the genomic structure and regulatory elements of the mouse GHR/BP gene, including unique exons and promoter regions.

Main Methods:

  • Cloning of mouse GHR/BP coding exons and the 5'UTR L2 exon.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) to analyze exon 4B presence.
  • Sequence analysis of the 5' flanking region of the 5'UTR L2 exon.
  • Ribonuclease protection assays to determine tissue-specific expression of 5'UTR variants.

Main Results:

  • Identified 11 coding exons in the mouse GHR/BP gene, with novel exons 4B and 8A.
  • Exon 4B is constitutively present in mouse GHR and GHBP mRNA, encoding a unique ligand-binding domain segment.
  • Exon 8A encodes the GHBP hydrophilic tail and 3'UTR.
  • The 5'UTR L2 exon and its GC-rich promoter show conservation with other species, despite a LINE-1 insertion upstream.
  • 5'UTR L2 is widely expressed, with 5'UTR L1 predominant in pregnant liver.

Conclusions:

  • The mouse GHR/BP gene possesses unique structural features, including novel exons, contributing to transcript diversity.
  • The characterized promoter elements and conserved regions suggest regulatory mechanisms for GHR/BP gene expression.
  • Understanding these structural and regulatory aspects is vital for deciphering GHR/BP function in growth and metabolism.

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