Mol._Cell._Biol.-2012-Eaton-1017-29.pdf (1.99 MB)
New mutations at the imprinted Gnas cluster show gene dosage effects of Gsa in postnatal growth and implicate XLas in bone and fat metabolism, but not in suckling
journal contribution
posted on 2023-06-08, 07:13 authored by Mark Maconochie, E Sally, W Christine, B Simon, B Colin, M Lee, E Jessica, T Lydia, P JoThe imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLas, XLN1, and ALEX or a double dose of maternally expressed Gsa 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 Gsa, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsa and loss of expression of XLas 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 (XLas, 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 XLas. This is, to our knowledge, the first report describing a role for XLas in bone metabolism. We propose that XLas is involved in the regulation of bone and adipocyte metabolism.
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- Published
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- Published version
Journal
Molecular and Cellular BiologyISSN
1098-5549Publisher
American Society for MicrobiologyExternal DOI
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5Volume
32Page range
1017-1029Department affiliated with
- Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2013-04-26First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-08-17Usage metrics
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