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3' Enhancer Drives Active and Untemplated Somatic Hypermutation of a
1 Transgene1

Departments of
*
Molecular Biophysics and Biochemistry and
Genetics, Yale University, New Haven, CT 06520
Somatic hypermutation is a highly regulated process that targets
mutations to the rearranged Ig genes. Little is known about the
cis-elements required for somatic hypermutation of the
light chain gene. We have studied somatic hypermutation of a
rearranged
1 transgene under the control of either a
2-4 or
3' enhancer. The mutations in the transgenes
were analyzed by sequencing DNA amplified from hypermutating Peyers
patch B cells. The results indicate that the
3' enhancer can drive
active hypermutation of a
1 transgene in Peyers patch
cells. The
1 transgene under analysis carried two marked
V
2 genes immediately upstream that could serve as
sequence donors in possible gene conversion events. There was no
evidence of sequence transfer to the hypermutated
1
gene, suggesting that gene conversion is not a major mechanism for
somatic hypermutation in mice.
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