Mea2/Golga3 gene is disrupted in a line of transgenic mice with a reciprocal translocation between Chromosomes 5 and 19 and is responsible for a defective spermatogenesis in homozygotes

A line of transgenic mouse T604 transmitted a transgene to progeny together with a set of chromosomes with a reciprocal translocation. The transgene w as integrated at a single site in the translocated chromosomes, as revealed by fluorescence in situ hybridization. The transgenic hemizygous males, al so heterozygous for the translocation of chromosomes, showed apparently nor mal spermatogenesis, while the males homozygous for the transgene as well a s for the translocated chromosomes showed a defect in spermatogenesis. Cons idering that the genetic rearrangement by either insertion of the transgene or the chromosome translocation in the T604 mouse line might have caused a recessive mutation in a gene indispensable for spermatogenesis, we have ma pped the transgene integration site and the translocation breakpoints in mo use chromosomes. Linkage analysis with SSLP markers showed that the loci fo r the transgene and the translocation breakpoints were closely located to D 5Mit24 on Chromosome (Chr) 5, and to a region between D19Mit19 and D19Jpk2 on Chr 19. Mea2 gene, mapped only 2 cM from D5Mit24 and known to show male- specific enhanced expression in the testis, was analyzed as a candidate for the gene disrupted in T604 transgenic mice. Southern blot analysis reveale d that Mea2 gene was indeed disrupted in T604 mice, and Northern blot analy sis of the testis RNA showed that the expression of Mea2 was annihilated in the testis of T604 transgenic homozygotes.