Loss-of-imprinting of Peg1 in mouse interspecies hybrids is correlated with altered growth

Abstract

Previous studies have shown that loss-of-imprinting (LOI) is a regular occurrence in interspecies hybrids of the genus Peromyscus. Furthermore, evidence was presented that indicated that LOI is involved in a placental hybrid dysgenesis effect resulting in abnormal placental growth and thus possibly in speciation. We show here that LOI of the strictly paternally expressed gene Peg1 (also called Mest) occurs in F1 hybrids between Mus musculus (MMU) and M. spretus (MSP). Peg1 LOI is correlated with increased body weight and increased weight of two of the organs tested, kidney and spleen. X-gal staining of tissues derived from Peg1(+/-) x MSP F1 mice, carrying a maternal LacZ knock-in allele of Peg1, demonstrates that LOI is stochastic in that it affects different tissues to variable extents and that, even within one tissue, not all cells are similarly affected. Furthermore, this expression from the maternal allele does not necessarily follow the endogenous paternal Peg1 expression pattern. Our results indicate that LOI occurs in interspecies hybrids in the genus Mus and that altered growth is a frequent outcome of LOI.