GLOMERULAR-SPECIFIC IMPRINTING OF THE MOUSE GS-ALPHA GENE - HOW DOES THIS RELATE TO HORMONE RESISTANCE IN ALBRIGHT HEREDITARY OSTEODYSTROPHY

The gene for alpha-stimulating guanine-nucleotide binding polypeptide, Gnas, has been considered as a candidate for the imprinting effects a scribed to distal mouse Chromosome (Chr) 2. Its human homologue (GNAS1 ) appears, from clinical and biochemical studies of patients with Albr ight hereditary osteodystrophy, to be paternally imprinted. GNAS1 maps to 20q13, a region that shows linkage conservation with distal mouse Chr 2. Ne have mapped Gnas within the imprinting region on distal Chr 2 by linkage analysis. To establish if Gnus is imprinted, we have look ed for expression differences in tissues taken horn mice carrying mate rnal duplication/paternal deficiency for distal Chr 2 (MatDp2) and its reciprocal (PatDp2). RNA in situ hybridization revealed high levels o f Gnas mRNA in glomeruli of PatDp2 embryos at late gestation and lower levels in glomeruli of MatDp2 embryos. These results strongly suggest that Gnas is maternally imprinted and suggest that the mouse gene may be imprinted in a manner opposite that predicted in human. (C) 1996 A cademic Press, Inc.