THE MOUSE INSULIN-LIKE GROWTH-FACTOR TYPE-2 RECEPTOR IS IMPRINTED AND CLOSELY LINKED TO THE TME LOCUS

T-ASSOCIATED maternal effect (Tme) is the only known maternal-effect mutation in the mouse1,2. The defect is nuclear-encoded3 and embryos that inherit a deletion of the Tme locus from their mother die at day 15 of gestation4. There are many genomically imprinted regions known in the mouse genome5,6, but so far no imprinted genes have been cloned. The Tme locus is absent in two chromosome-17 deletion mutants, T(hp) and the t(Lub2), and its position has been localized using these deletions to a 1-cM region7-10. We report here that the genes for insulin-like growth factor type-2 receptor (Igf2r) and mitochondrial superoxide dismutase-2 (Sod-2) are absent from both deletions. Probes for these genes and for plasminogen (Plg) and T-complex peptide 1 (Tcp-1) were used in pulsed-field gel mapping to show that Tme must lie within a region of 800-1,100 kb. We also demonstrate that embryos express Igf2r only from the maternal chromosome, and that Tcp-1, Plg and Sod-2 are expressed from both chromosomes. Therefore Igf2r is imprinted and closely linked or identical to Tme.