137. GENOMIC IMPRINTING IN THE MARSUPIAL MAMMARY GLAND

Abstract

Genomic imprinting is an epigenetic mechanism that differentially regulates the expression of certain genes, resulting in expression from only one parental allele. In mammals, genomic imprinting occurs in the placenta of both eutherians and marsupials, and plays an important role in regulating nutrition and growth of the developing fetus. The mammary gland also provides a critical source of nutrition for the neonate in all mammals, but there are few imprinting studies of this organ. Marsupials deliver tiny, altricial young that complete development during an extended lactation. INS (insulin) is paternally expressed in the eutherian and marsupial yolk sac and curiously is the only gene that is solely imprinted in this organ (1, 2). Insulin regulates carbohydrate metabolism, protein synthesis and cell growth. Insulin, (plus cortisol and prolactin) is required for the onset of lactation and the synthesis of milk (3). We characterised INS expression and examined its imprint status in the mammary gland of the tammar wallaby. INS mRNA is expressed in the mammary gland of the tammar from birth and throughout of lactation with highest expression at the initiation of lactation (Phase 1-2a) and around Phase 3 of lactation. Direct sequencing of 7 individuals at various stages of lactation confirmed that INS is imprinted in the mammary gland. Surprisingly, INS may also be imprinted in several other organs in the adult and juvenile wallaby. Preliminary bisulfite sequencing suggests there is a differentially methylated region located upstream of INS which may help to regulate INS expression. This is the first study to identify INS imprinting outside the yolk sac. As INS is critical for lactation, this is also the first indication that genomic imprinting may regulate lactation, suggesting that imprinting in the mammary gland may be as critical for post-natal survival as placental imprinting is for pre-natal development. (1) Deltour LX, et al. (1995). Tissue- and developmental stage-specific imprinting of the mouse proinsulin gene, Ins2. Dev Biol 168(2): 686–688.(2) Ager EI, et al. (2007). Insulin is imprinted in the placenta of the marsupial, Macropus eugenii. Dev Biol 309: 317–328.(3) Bolander FF, et al. (1981). Insulin is essential for accumulation of casein mRNA in mouse mammary epithelial cells. Proc Natl Acad Sci USA 78(9): 5682–5684.