Rearrangement and expression of immunoglobulin genes in transgenic mice.
Transgenic mice are discussed which carry a rearrangement test transgene. The methylation status of the transgene varies, depending on the background mouse strain. When the transgene is bred into the C57BL/6 strain, it is completely methylated and not rearranged in lymphoid organs. After several generations of crossing into DBA/2 or SJL the transgene becomes unmethylated and rearranges at high frequency. A strain specific modifier of DNA methylation (Ssm-1) was mapped close to the Friend virus susceptibility locus (Fv-1) on mouse chromosome 4. Rearranged transgenes from spleen, bone marrow and thymus of adult mice or fetal liver were cloned and sequenced. A great variety of joints was found, with about 1/3 being in the correct reading frame. Small deletions into the V- and J-coding ends as well as N region additions contributed to the variability. The fetal joints showed no N regions. Since no functional immunoglobulin (Ig) gene can be created from this artificial test gene, the data indicate that the rearrangement mechanism of the fetus differs from that of the adult.
Storb
U
U
Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
Engler
P
P
Klotz
E
E
Weng
A
A
Haasch
D
D
Pinkert
C
C
Doglio
L
L
Glymour
M
M
Brinster
R
R
D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D008297:Male; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D010375:Pedigree
D004247:DNA