Mammalian cells that have undergone gene amplification and/or gene rea
rrangement have been used as resources to gain insight into the questi
ons of chromosome structure and dynamics, The multidrug resistant muri
ne cell line J7.V2-1 has been shown previously to contain two distinct
forms of the highly amplified mdr2 gene, a member of the mouse gene f
amily responsible for the multidrug resistant (MDR) phenotype [Kirschn
er, L. S. (1995) DNA Cell Biol, 14, 47-59], Characterization of both f
orms of the gene revealed that one form corresponded to the wild-type
structure of the gene, whereas the other represented a rearrangement,
Investigation of this altered gene demonstrated a deletion of 1.6 kb o
f the wild-type sequence, and replacement of this region with a poly(A
T) tract that appears to have been generated de novo, Analysis of the
native sequence in this region demonstrated the absence of repetitive
elements, but was notable for the presence of two long stretches of po
lypurine:polypyrimidine strand asymmetry. Analysis of mdr2 transcripts
in this cell line revealed that nearly all of the mRNA is transcribed
from the rearranged form of the gene. This message is unable to code
for a functional mdr2 gene product, owing to a deletion of the fourth
exon during this event. Mechanisms of the rearrangement, as well as th
e significance of this curious effect on transcription, are discussed.