In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 20 ( 2005-05-17), p. 7386-7391
Abstract:
Gnas is an imprinted gene with multiple gene products resulting from alternative splicing of different first exons onto a common exon 2. These products include stimulatory G protein α-subunit (G s α), the G protein required for receptor-stimulated cAMP production; extralarge G s α (XLαs), a paternally expressed G s α isoform; and neuroendocrine-specific protein (NESP55), a maternally expressed chromogranin-like protein. G s α undergoes tissue-specific imprinting, being expressed primarily from the maternal allele in certain tissues. Heterozygous mutation of exon 2 on the maternal (E2 m-/+ ) or paternal (E2 +/p- ) allele results in opposite effects on energy metabolism. E2 m-/+ mice are obese and hypometabolic, whereas E2 +/p- mice are lean and hypermetabolic. We now studied the effects of G s α deficiency without disrupting other Gnas gene products by deleting G s α exon 1 (E1). E1 +/p- mice lacked the E2 +/p- phenotype and developed obesity and insulin resistance. The lean, hypermetabolic, and insulin-sensitive E2 +/p- phenotype appears to result from XLαs deficiency, whereas loss of paternal-specific G s α expression in E1 +/p- mice leads to an opposite metabolic phenotype. Thus, alternative Gnas gene products have opposing effects on glucose and lipid metabolism. Like E2 m-/+ mice, E1 m-/+ mice had s.c. edema at birth, presumably due to loss of maternal G s α expression. However, E1 m-/+ mice differed from E2 m-/+ mice in other respects, raising the possibility for the presence of other maternal-specific gene products. E1 m-/+ mice had more severe obesity and insulin resistance and lower metabolic rate relative to E1 +/p- mice. Differences between E1 m-/+ and E1 +/p- mice presumably result from differential effects on G s α expression in tissues where G s α is normally imprinted.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0408268102
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2005
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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