Endocrine Abstracts

Mouse distal Chromosome 2 has a proximal region containing a single imprinted gene, Neuronatin, Nnat. In situ hybridisation has shown strong expression of neuronatin in the embryonic mouse Rathke's pouch and primordial anterior pituitary (Wijnholds et al 1995, Dev Biol 171:73-84) and has been proposed to participate in pituitary development. Uniparental maternal inheritance of the proximal region leads to decreased folding of the cerebellum (Kikyo et al 1997, Dev Biol 190:66-7) an effect attributed to lack of expression of neuronatin, which is expressed exclusively from the paternally derived allele. We have now investigated the effect on the pituitary when the Nnat region is solely paternally or maternally derived. Pituitary area was determined from digital images using imaging software (Scanalytics Inc) in male newborn (i) wild type (WT) mice, (ii) mice with two paternally derived copies of the region and therefore two expressed copies of Nnat (paternal duplication, PatDp), and (iii) mice with two maternally derived copies of the region and therefore no expressed Nnat (maternal duplication, MatDp). In addition, anterior pituitary tissue was examined by electron microscopy to determine the number and size of somatotrophs and lactotrophs (identified by immunogold labelling for GH and PRL respectively). Pituitary area was significantly reduced in PatDp mice, 57 +/- 2.9% (n=10, P<0.01) compared to WT. Somatotroph and lactotroph number were significantly reduced as a proportion of total cells (3 +/- 0.5 % Pat Dp vs 31 +/- 3% WT and 5 +/- 1% vs 29 +/- 2% WT respectively; P<0.01,n=5). Cell size was also reduced. However pituitary area, somatotroph and lactotroph number and cell size were not significantly different in MatDp mice compared to WT. These data suggest that overexpression of Nnat (PatDp) represses normal pituitary differentiation but in contrast lack of Nnat (MatDp) does not have consequences for cell differentiation and pituitary size.