Mice maintain predominantly maternal G?s expression throughout life in brown fat tissue (BAT), but not other tissues.

ABSTRACT: The murine Gnas (human GNAS) locus gives rise to G?s and different splice variants thereof. The G?s promoter is not methylated thus allowing biallelic expression in most tissues. In contrast, the alternative first Gnas/GNAS exons and their promoters undergo parent specific methylation, which limits transcription to the non-methylated allele. Pseudohypoparathyroidism type Ia (PHP1A) or type Ib (PHP1B) are caused by heterozygous maternal GNAS mutations suggesting that little or no G?s is derived in some tissues from the non-mutated paternal GNAS thereby causing hormonal resistance. Previous data had indicated that G?s is mainly derived from the maternal Gnas allele in brown adipose tissue (BAT) of newborn mice, yet it is biallelically expressed in adult BAT. This suggested that paternal G?s expression is regulated by an unknown factor(s) that varies considerably with age. To extend these findings, we now used a strain-specific SNP in Gnas exon 11 (rs13460569) for evaluation of parent-specific G?s expression through the densitometric quantification of BanII-digested RT-PCR products and digital droplet PCR (ddPCR). At all investigated ages, G?s transcripts were derived in BAT predominantly from the maternal Gnas allele, while kidney and liver showed largely biallelic G?s expression. Only low or undetectable levels of other paternally Gnas-derived transcripts were observed, making it unlikely that these are involved in regulating paternal G?s expression. Our findings suggest that a cis-acting factor could be implicated in reducing paternal G?s expression in BAT and presumably in proximal renal tubules, thereby causing PTH-resistance if the maternal GNAS/Gnas allele is mutated.

SUBMITTER: Tafaj O 

PROVIDER: S-EPMC5943706 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature