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首页> 外文期刊>Genomics >The imprinted oedematous-small mutation on mouse chromosome 2 identifies new roles for gnas and gnasxl in development.
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The imprinted oedematous-small mutation on mouse chromosome 2 identifies new roles for gnas and gnasxl in development.

机译：小鼠染色体2上的印迹水肿小突变确定了gnas和gnasxl在发育中的新作用。

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摘要

The Gnas locus is highly complex and encodes several oppositely imprinted and alternatively spliced transcripts. Gnas itself encodes Gsalpha, which is involved in endocrine function and bone development, but the roles for the other transcripts have not been established. Here we describe a mouse mutation that provides further biological functions for the Gnas locus. The mutation Oed-Sml, induced by ethylnitrosourea (ENU), has been mapped to the distal chromosome 2 imprinting region that includes Gnas. The mutation displays two distinct phenotypes dependent on parental origin. When the mutation is maternally transmitted, a microcardia with gross edema (Oed) results. By contrast, when the mutation is paternally transmitted, a growth retardation (Sml) is seen that becomes evident within 5 days of birth. Here we show Oed-Sml to be a point mutation in Gnas exon 6, resulting in a valine to glutamate substitution at residue 159 (V159E). Both maternal- and paternal-specific transcripts derive from this missense mutation. The maternally expressed mutant Gnas transcript is the candidate for Oed and the paternally expressed mutant Gnasxl transcript is the candidate for Sml. We propose a new role for Gnas in heart growth and a role for Gnasxl in postnatal growth. These findings potentially have implications for human Albright hereditary osteodystrophy, a condition caused by mutations in GNAS.
机译：Gnas基因座非常复杂，并编码几个相反的印迹和剪接的转录本。 Gnas本身编码Gsalpha，Gsalpha参与内分泌功能和骨骼发育，但尚未确定其他转录本的作用。在这里，我们描述了一种为Gnas基因座提供进一步生物学功能的小鼠突变。由乙基亚硝基脲（ENU）诱导的Oed-Sml突变已定位到包含Gnas的远端2号染色体印迹区域。该突变表现出两种不同的表型，取决于父母的起源。当突变由母体传播时，会导致微心大水肿（Oed）。相比之下，当突变是父系传播时，可以看到生长迟缓（Sml）在出生后5天内变得明显。在这里，我们显示Oed-Sml是Gnas外显子6中的点突变，导致在残基159（V159E）上缬氨酸被谷氨酸取代。母本和父本特异的转录本均来自这种错义突变。母本表达的突变体Gnas转录物是Oed的候选物，而母本表达的突变体Gnasxl转录物是Sml的候选物。我们提出了Gnas在心脏生长中的新作用以及Gnasxl在产后生长中的作用。这些发现可能对人的奥尔布赖特遗传性骨营养不良症有影响，这是由GNAS突变引起的。

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