Rearrangement and expression of immunoglobulin genes in transgenic mice

• Published in: Current topics in microbiology and immunology Vol. 182; p. 137
• Main Authors: Storb, U, Engler, P, Klotz, E, Weng, A, Haasch, D, Pinkert, C, Doglio, L, Glymour, M, Brinster, R
• Format: Journal Article
• Language: English
• Published: Germany 1992
• Subjects: Animals; DNA - chemistry; DNA - genetics; Female; Gene Expression; Gene Rearrangement; Genes, Immunoglobulin; Male; Methylation; Mice; Mice, Transgenic; Pedigree
• ISSN: 0070-217X
• DOI: 10.1007/978-3-642-77633-5_16

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.