Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-9-22
pubmed:abstractText
Previous work on the cis-acting elements that control heavy chain variable region (VH) gene somatic hypermutation has indicated the presence of an as yet unidentified element(s) 3' of the intron enhancer that is necessary for high rate mutation. Examination of cis-acting elements involved in kappa light chain V gene hypermutation has demonstrated a requirement for both the intronic and 3' kappa enhancers in this process. To examine whether the 3'alpha heavy chain enhancer [3'alpha E(hs1,2)] is required for somatic hypermutation of VH genes, we generated two types of transgenic mice. One type was generated using a construct containing a VH promoter, a rearranged VDJ, the heavy chain intronic enhancer, and the murine heavy chain 3'alpha E(hs1,2). The transgenes in the second lines were similar to the transgenes in the first with the addition of a second complete matrix attachment region (MAR) 3' of the heavy chain intronic enhancer, and splice acceptor and polyadenylation sites between the two enhancers. Analysis of both transgenes revealed levels of mutation at least 10-fold lower than endogenous VH genes. These data suggest that the 3'alpha E(hs1,2) does not play a role analogous to the 3' kappa enhancer in the regulation of the hypermutation process. Moreover, in one of the transgenes, the presence of the 3'alpha E(hs1,2) resulted in a lack of transcription in vivo, suggesting a negative regulatory role for this enhancer in certain contexts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
367-78
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9293770-Animals, pubmed-meshheading:9293770-B-Lymphocytes, pubmed-meshheading:9293770-Enhancer Elements, Genetic, pubmed-meshheading:9293770-Genes, Immunoglobulin, pubmed-meshheading:9293770-Haptens, pubmed-meshheading:9293770-Hybridomas, pubmed-meshheading:9293770-Immunoglobulin Heavy Chains, pubmed-meshheading:9293770-Immunoglobulin Variable Region, pubmed-meshheading:9293770-Mice, pubmed-meshheading:9293770-Mice, Inbred A, pubmed-meshheading:9293770-Mice, Inbred BALB C, pubmed-meshheading:9293770-Mice, Inbred C57BL, pubmed-meshheading:9293770-Mice, Transgenic, pubmed-meshheading:9293770-Mutation, pubmed-meshheading:9293770-Nitrophenols, pubmed-meshheading:9293770-Peyer's Patches, pubmed-meshheading:9293770-Phenylacetates, pubmed-meshheading:9293770-Transcription, Genetic, pubmed-meshheading:9293770-Transgenes, pubmed-meshheading:9293770-p-Azobenzenearsonate
pubmed:year
1997
pubmed:articleTitle
Evaluation of the role of the 3'alpha heavy chain enhancer [3'alpha E(hs1,2)] in Vh gene somatic hypermutation.
pubmed:affiliation
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson Medical College, Philadelphia, PA 19107, U.S.A.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't