ASSOCIATION OF A REDEFINED PROXIMAL MOUSE-CHROMOSOME-1 IMPRINTING REGION AND U2AFBP-RS U2AF1-RS1 EXPRESSION/

Mice with maternal and paternal disomy for chromosome 11 (Chr 11) show growth retarded and overgrowth phenotypes, respectively, which can be attributed to genomic imprinting. Previous studies have defined the r egion of Chr 11 responsible (the Chr 11 imprinting region) as lying pr oximal to the T30H translocation breakpoint at the borders of G-bands 11B1.2 and 11B1.3. Evidence is presented here with two new translocati ons, T57H and T41Ad, which sequentially reduce the size of the imprint ing region and locate it proximal to the T41Ad breakpoint in G-band 11 A3.2. It therefore lies close to the centromere. The imprinted gene, U 2af1-rs1, is known to be located within the original region and has be en regarded as a candidate for the imprinting effects. Meiotic and mit otic chromosome FISH analysis, together with U2af1-rs1 expression stud ies are now described which show that the gene lies within the newly d efined imprinting region and that its expression levels relate to the presence/absence and number of functional paternal alleles. U2af1-rs1 therefore remains a candidate gene for the Chr 11 imprinting effects. However, another recently reported imprinted gene, Meg1/Grb10, that li es within the region is also a good candidate, as it encodes a growth factor receptor. Meg1/Grb10 maps about 15 cM from U2af1-rs1 and is sep arated by conserved regions showing homology with two different human chromosomes. For these reasons, and because the two human homologues o f U2af1-rs1 and Meg1/Grb10 also lie on different chromosomes, it would seem likely that the two genes identify two distinct imprinting domai ns within the small proximal region of mouse Chr 11.