|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 188, Number 8, October 19, 1998 1421-1431
By
§§
From * The Howard Hughes Medical Institute and The 40-kb region downstream of the most 3' immunoglobulin (Ig) heavy chain constant region gene (C The Children's Hospital, Boston, Massachusetts
02115; and the § Center for Blood Research and Department of Genetics, Harvard Medical School,
Boston, Massachusetts 02115
) contains a series of transcriptional enhancers speculated to play a role in Ig
heavy chain class switch recombination (CSR). To elucidate the function of this putative CSR
regulatory region, we generated mice with germline mutations in which one or the other of
the two most 5' enhancers in this cluster (respectively referred to as HS3a and HS1,2) were replaced either with a pgk-neor cassette (referred to as HS3aN and HS1,2N mutations) or with a
loxP sequence (referred to as HS3a
and HS1,2, respectively). B cells homozygous for the
HS3aN or HS1,2N mutations had severe defects in CSR to several isotypes. The phenotypic
similarity of the two insertion mutations, both of which were cis-acting, suggested that inhibition might result from pgk-neor cassette gene insertion rather than enhancer deletion. Accordingly, CSR returned to normal in B cells homozygous for the HS3a or HS1,2 mutations. In
addition, induced expression of the specifically targeted pgk-neor genes was regulated similarly
to that of germline CH genes. Our findings implicate a 3' CSR regulatory locus that appears remarkably similar in organization and function to the 
-globin gene 5' LCR and which we
propose may regulate differential CSR via a promoter competition mechanism.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
