Mammalian body size is regulated by both genetic and environmental factors. Minoo Rassoulzadegan and colleagues now add to this list a heritable epigenetic mechanism (paramutation) that results in increased body size (see ). When injecting the microRNA miR-124, which is normally expressed in the central nervous system, into fertilised mouse eggs, the researchers found an unexpected 30% increase in body size of the resulting mice, which persisted into adulthood. Interestingly, this increased growth was evident very early in development, with frequent blastocyst inner cell mass duplications causing a rise in twin pregnancies. The progeny of miR-124-injected males inherited the increased body size; this inheritance correlated with the presence of miR-124 in the sperm. The researchers identified a candidate miR-124-induced paramutation in the form of a heritable chromatin modification in Sox9, which encodes a transcription factor involved in regulating embryonic proliferation and differentiation. From their findings, they propose that RNA-mediated paramutations might contribute to other heritable traits that Mendelian genetics cannot explain.
