| First Author | Eaton SA | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 5 | Pages | 1017-29 |
| PubMed ID | 22215617 | Mgi Jnum | J:182868 |
| Mgi Id | MGI:5317009 | Doi | 10.1128/MCB.06174-11 |
| Citation | Eaton SA, et al. (2012) New mutations at the imprinted Gnas cluster show gene dosage effects of Gsalpha in postnatal growth and implicate XLalphas in bone and fat metabolism but not in suckling. Mol Cell Biol 32(5):1017-29 |
| abstractText | The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLalphas, XLN1, and ALEX or a double dose of maternally expressed Gsalpha to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsalpha, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsalpha and loss of expression of XLalphas and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLalphas, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLalphas. This is, to our knowledge, the first report describing a role for XLalphas in bone metabolism. We propose that XLalphas is involved in the regulation of bone and adipocyte metabolism. |
