A, Breeding schemes for generation of maintenance (monoallelic Igf2) and loss of imprinting (biallelic Igf2) mice. Maternal transmission of 142* mutation (H19-ICR +/−) results in biallelic expression in offspring by abolishing CTCF insulator activity at the normally silenced maternal allele. Paternal transmission leads to the typical monoallelic expression. B, Ventral prostate (VP) and Dorsolateral prostate (DLP) tissues were analyzed for maintenance of imprinting (MOI) and loss of imprinting (LOI) in mice and maternal and paternal allelic expression was quantitated using FluPE as described in methods. MOI mice maintain expression from a single allele, while LOI mice exhibit biallelic expression. C,
Igf2 mRNA expression measured by qPCR in mouse prostates (*P<0.05, mean+SD; n = 6 each group). D, Body weights of experimental animals were recorded throughout their lifetime. LOI animals expressing biallelic Igf2 were persistently heavier throughout their life (mean+95% CI; **P<0.01, *P<0.05). E, F, G,
Igf2 protein expression was quantitatively analyzed on tissue microarrays constructed from mouse prostate tissues. Igf2 protein expression was significantly elevated in LOI animals with (E)
Nkx3.1+/+ (P=0.001, P=0.015, P=0.012; 6, 12, 18 months), (F)
Nkx3.1+/− (P=0.002, P=0.02, P=0.04; 6, 12, 18 months) and (G)
Nkx3.1−/− (P<0.001, P=0.029, P=0.043; 6, 12, 18 months), backgrounds across all ages (*P<0.05, columns represent Mean+SD; n > 8 for each group).