SOMATIC RECOMBINATION OF HEAVY-CHAIN VARIABLE REGION TRANSGENES WITH THE ENDOGENOUS IMMUNOGLOBULIN HEAVY-CHAIN LOCUS IN MICE

被引:25
作者
GIUSTI, AM [1 ]
COFFEE, R [1 ]
MANSER, T [1 ]
机构
[1] THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107
关键词
TRANSGENIC MICE; ANTIBODY GENES;
D O I
10.1073/pnas.89.21.10321
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transgenic lines of mice were derived by using plasmid constructs containing DNA encoding an antibody heavy chain variable-diversity-joining region (V(H)-D-J(H)) and various amounts of 5' and 3' flanking DNA but tacking any repetitive isotype switch (S) or constant (C) region DNA. Unexpectedly, many of the antibody V(H) regions expressed by B-cell hybridomas generated from immunized transgenic mice were found to be of transgenic origin. Further analyses showed that somatic events had generated hybrid genomic loci in the mice containing the transgenic V(H)-D-J(H) gene and plasmid sequences 5' of endogenous heavy chain C region genes. Thus, V(H)-D-J(H) transgenes lacking S and C region DNA can recombine with endogenous Igh DNA, leading to the expression of transgene-encoded antibody.
引用
收藏
页码:10321 / 10325
页数:5
相关论文
共 26 条
[1]   JOINING OF IMMUNOGLOBULIN HEAVY-CHAIN GENE SEGMENTS - IMPLICATIONS FROM A CHROMOSOME WITH EVIDENCE OF 3 D-JH FUSIONS [J].
ALT, FW ;
BALTIMORE, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (13) :4118-4122
[2]   GENE REPLACEMENT WITH ONE-SIDED HOMOLOGOUS RECOMBINATION [J].
BERINSTEIN, N ;
PENNELL, N ;
OTTAWAY, CA ;
SHULMAN, MJ .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (01) :360-367
[3]   IMMUNOGLOBULIN GENE-TRANSCRIPTION - MOLECULAR MECHANISMS [J].
CALAME, KL .
TRENDS IN GENETICS, 1989, 5 (12) :395-399
[4]   A MOUSE IMMUNOGLOBULIN HEAVY-CHAIN DELETION MUTANT - ISOLATION OF A CDNA CLONE AND SEQUENCE-ANALYSIS OF THE MESSENGER-RNA [J].
DUNNICK, W ;
RABBITTS, TH ;
MILSTEIN, C .
NUCLEIC ACIDS RESEARCH, 1980, 8 (07) :1475-1484
[5]   RAPID PRODUCTION OF FULL-LENGTH CDNAS FROM RARE TRANSCRIPTS - AMPLIFICATION USING A SINGLE GENE-SPECIFIC OLIGONUCLEOTIDE PRIMER [J].
FROHMAN, MA ;
DUSH, MK ;
MARTIN, GR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :8998-9002
[6]   ISOTYPE SWITCHING OF AN IMMUNOGLOBULIN HEAVY-CHAIN TRANSGENE OCCURS BY DNA RECOMBINATION BETWEEN DIFFERENT CHROMOSOMES [J].
GERSTEIN, RM ;
FRANKEL, WN ;
HSIEH, CL ;
DURDIK, JM ;
RATH, S ;
COFFIN, JM ;
NISONOFF, A ;
SELSING, E .
CELL, 1990, 63 (03) :537-548
[7]  
HOGAN B, 1986, MANIPULATING MOUSE E, P79
[8]  
JESKE D, 1986, J IMMUNOL, V136, P2568
[9]  
KATZENBERG DR, 1988, J IMMUNOL, V140, P3219
[10]   RECOMBINATION BETWEEN AN EXPRESSED IMMUNOGLOBULIN HEAVY-CHAIN GENE AND A GERMLINE VARIABLE GENE SEGMENT IN A LY-1+ B-CELL LYMPHOMA [J].
KLEINFIELD, R ;
HARDY, RR ;
TARLINTON, D ;
DANGL, J ;
HERZENBERG, LA ;
WEIGERT, M .
NATURE, 1986, 322 (6082) :843-846