A strain-specific modifier on mouse chromosome 4 controls the methylation of independent transgene loci

Peter Engler*, Deanna Haasch, Carl A. Pinkert, Lynn Doglio, Medellena Glymour, Ralph Brinster, Ursula Storb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

A transgene, pHRD, is highly methylated in 12 independent mouse lines when in a C57BL/6 strain background, but becomes progressively less methylated when bred into a DBA/2 background. Transgenes inherited from the mother are generally more methylated; however, this parental effect disappears following continued breeding into the nonmethylating strain. Mapping experiments using BXD recombinant inbred mice as well as other inbred strains indicate that a single strain-specific modifier (Ssm-1) linked to, but distinct from, Fv-1 is responsible for the strain effect. In addition to the methylated and unmethylated transgenic phenotypes, certain mice exhibit a partial methylation pattern that is a consequence of an unusual cellular mosaicism. The pHRD transgene, containing target sequences for the V(D)J recombinase, undergoes site-specific recombination only in lymphoid tissues. This V-J joining is restricted primarily to unmethylated transgene copies.

Original languageEnglish (US)
Pages (from-to)939-947
Number of pages9
JournalCell
Volume65
Issue number6
DOIs
StatePublished - Jun 14 1991

Funding

We are especially grateful to W. Reik for several key suggestions during the course of this work. We would also like to express our gratitude to D. Lo for help with the initial analysis of the transgenic mice, to D. Gottschling, C. Laird, R. Braun, J. Spofford, and B. Taylor for helpful comments on this work, and to D. Solter, M. Gellert, and A. Weng for suggestions about the manuscript. We also acknowledge the contributions of G. Eozek for her assistance with the maintenance of the mouse colony. This work has been supported by NIH grants Al24780 and HD23089. P. E. was supported by NIH postdoctoral training grant HD07136 and L. D. byafellowship from the National Multiple Sclerosis Society.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'A strain-specific modifier on mouse chromosome 4 controls the methylation of independent transgene loci'. Together they form a unique fingerprint.

Cite this