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

Cell. 1991 Jun 14;65(6):939-47. doi: 10.1016/0092-8674(91)90546-b.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatin / ultrastructure
  • Chromosome Mapping
  • DNA / metabolism*
  • Gene Rearrangement*
  • Methylation
  • Mice
  • Mice, Inbred C57BL / genetics*
  • Mice, Transgenic
  • Mosaicism
  • Pedigree


  • Chromatin
  • DNA