| First Author | Tafaj O | Year | 2017 |
| Journal | Bone | Volume | 103 |
| Pages | 177-187 | PubMed ID | 28694163 |
| Mgi Jnum | J:257079 | Mgi Id | MGI:6112808 |
| Doi | 10.1016/j.bone.2017.07.001 | Citation | Tafaj O, et al. (2017) Mice maintain predominantly maternal Galphas expression throughout life in brown fat tissue (BAT), but not other tissues. Bone 103:177-187 |
| abstractText | The murine Gnas (human GNAS) locus gives rise to Galphas and different splice variants thereof. The Galphas 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 Galphas is derived in some tissues from the non-mutated paternal GNAS thereby causing hormonal resistance. Previous data had indicated that Galphas 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 Galphas 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 Galphas expression through the densitometric quantification of BanII-digested RT-PCR products and digital droplet PCR (ddPCR). At all investigated ages, Galphas transcripts were derived in BAT predominantly from the maternal Gnas allele, while kidney and liver showed largely biallelic Galphas expression. Only low or undetectable levels of other paternally Gnas-derived transcripts were observed, making it unlikely that these are involved in regulating paternal Galphas expression. Our findings suggest that a cis-acting factor could be implicated in reducing paternal Galphas expression in BAT and presumably in proximal renal tubules, thereby causing PTH-resistance if the maternal GNAS/Gnas allele is mutated. |
