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Analysis of LINE-1 Retrotransposition at the Single Nucleus Level
11:52

Analysis of LINE-1 Retrotransposition at the Single Nucleus Level

Published on: April 23, 2016

The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn

J L Chu1, J Drappa, A Parnassa

  • 1Hospital for Special Surgery, Cornell University Medical Center, New York, New York 10021.

The Journal of Experimental Medicine
|August 1, 1993
PubMed

Insights

Mice with a Fas gene mutation exhibit reduced Fas mRNA and produce abnormal transcripts due to retrotransposon insertion. This defect in Fas expression leads to lymphoproliferation and autoimmunity in MRL/lpr mice.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Fas is a critical cell surface protein regulating lymphocyte apoptosis.
  • Mutations in the Fas gene cause lymphoproliferation (lpr) and autoimmunity in MRL/lpr mice.

Purpose of the Study:

  • To investigate the molecular basis of Fas gene dysfunction in MRL/lpr mice.
  • To analyze Fas mRNA expression levels and identify aberrant transcripts.

Main Methods:

  • Reverse transcriptase polymerase chain reaction (RT-PCR) for mRNA analysis.
  • Northern blotting to quantify Fas mRNA levels.
  • Molecular cloning and nucleotide sequencing of Fas-ETn chimeric cDNA.

Main Results:

  • MRL/lpr mice showed a 10-fold reduction in wild-type Fas mRNA compared to MRL mice.
  • Aberrant chimeric transcripts containing the early retrotransposon (ETn) were detected in MRL/lpr mice.
  • ETn insertion into a Fas gene intron and alternative splicing were identified as the cause.

Conclusions:

  • ETn retrotransposon insertion into the Fas gene intron disrupts normal mRNA production.
  • Alternative splicing induced by the ETn insertion leads to reduced wild-type Fas mRNA and aberrant transcripts.
  • These molecular defects in Fas expression underlie the lymphoproliferation and autoimmunity observed in MRL/lpr mice.

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