Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader–Willi syndrome

Morabito, Michael V.; Abbas, Atheir I.; Hood, Jennifer L.; Kesterson, Robert A.; Jacobs, Michelle M.; Kump, David S.; Hachey, David L.; Roth, Bryan L.; Emeson, Ronald B.

doi:10.1016/j.nbd.2010.04.004

Cited by 118 publications

(120 citation statements)

References 72 publications

(154 reference statements)

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“…Within this 62.5-Mb interval lay 358 protein-coding and 22 miRNA genes, three of which had previously been described to affect coat pigmentation when mutated in the mouse (Atp7a, Eda, and Htr2c). As a result of an absence of ectodermal dysplasia phenotypes [commonly associated with Eda mutants (34)] or postnatal growth retardation [as seen in an Htr2c mutant (35)], all coding exons and splice junctions of Atp7a were sequenced. A single T-to-C missense transition was detected at X:103283830, corresponding to position 1570 of the Atp7a transcript, in exon 5 of 23 total exons (Fig.…”

Section: Resultsmentioning

confidence: 99%

Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease

Siggs

Cruite

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Copper influences the pathogenesis of prion disease, but whether it is beneficial or detrimental remains controversial. Copper homeostasis is also essential for normal physiology, as highlighted by the spectrum of diseases caused by disruption of the copper transporting enzymes ATP7A and ATP7B. Here, by using a forward genetics approach in mice, we describe the isolation of three alleles of Atp7a , each with different phenotypic consequences. The mildest of the three, Atp7a brown , was insufficient to cause lethality in hemizygotes or mottling of the coat in heterozygotes, but did lead to coat hypopigmentation and reduced copper content in the brains of hemizygous males. When challenged with Rocky Mountain Laboratory scrapie, the onset of prion disease was delayed in Atp7a brown mice, and significantly less proteinase-resistant prion protein was found in the brains of moribund Atp7a brown mice compared with WT littermates. Our results establish that ATP7A-mediated copper homeostasis is important for the formation of pathogenic proteinase-resistant prion protein.

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Section: Resultsmentioning

confidence: 99%

Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease

Siggs

Cruite

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…5-HT receptor proteins were isolated from RPTCs as previously described (Morabito et al, 2010). A 30-mg sample of the resulting protein was then treated with either N-glycosidase F (PNGase) (New England BioLabs, Ipswich, MA) according to the manufacturer's instructions or temperaturematched control conditions for 2 hours, then loaded onto an SDS-PAGE gel.…”

Section: Methodsmentioning

confidence: 99%

5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists

Harmon

Wills

McOmish

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT 2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl) propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT 2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney.

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“…The density of 5-HT2C increases in VGV transgenic mice compared with wild-type mice (25). Although it is expected that responsiveness attenuates in the VGV type from the above-mentioned molecular knowledge, the 5-HT2C-related responses for the agonist actually increase in the VGV animal model.…”

Section: Rna Editing (Fig 1)mentioning

confidence: 96%

“…MBII-52 combines with the 5-HT2C mRNA in that region and promotes receptor-type splicing. In PraderWilli syndrome (PWS), which results in obesity, short stature, poor muscle tone and other symptoms, the genomic DNA domain encoding the MBII-52 (15q11-13 in human) is lacking (42); therefore, the editing and expression of 5-HT2C receptor-type mRNAs are influenced (25). Because the 5-HT2C knockout mouse becomes obese, the participation of these will be determined.…”

Section: Short Variant (Fig 2)mentioning

confidence: 99%

Serotonin 2C Receptor as a Superhero: Diversities and Talents in the RNA Universe for Editing, Variant, Small RNA and Other Expected Functional RNAs

Tohda

2014

J Pharmacol Sci

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The serotonin 2C receptor subtype (5-HT2C) seems to have various physiological roles in addition to the function of the receptor. The serotonin receptors are classified into many subtypes (1), especially more than 10 splicing variants have been reported for the 5-HT4 subtype (1, 2), which has been recently reported to be involved in the circadian clock (3, 4). Among the various serotonin receptor subtypes, 5-HT2C is especially interesting. The history of studies on 5-HT2C can also convey its distinct personality. We are often surprised and puzzled by novel discoveries about 5-HT2C. In this review, the "curriculum vitae" of 5-HT2C is first introduced, followed by a discussion of the unique world of 5-HT2C, including RNA editing, short variants, relationship with small RNA, therapeutic potential for functional mental disease (FMD) such as depression and schizophrenia, and the "friendship" with Wakan-yaku (Sino-Japanese traditional medicine). Curriculum vitae of 5-HT2C5-HT2C was previously named 5-HT 1C . Therefore, searches for papers about the receptor written before 1992 must use "5-HT 1C " as the keyword. The serotonin receptor was previously classified into 5-HT 1 and 5-HT 2 by the receptor's affinity for serotonin; 5-HT 1 has approximately 100 times greater affinity for serotonin than does 5-HT 2 . This is caused by the historical background when the "receptor binding assay" was the mainstream method of receptor studies. Each receptor subtype was further subdivided by drug affinities. Thereafter, when the mainstream experimental techniques shifted to second messenger systems, it was clarified that the 5-HT 1 group is coupled to the cAMP system and that the 5-HT 2 group is linked with the inositolphosphate turnover system. However, one subtype of 5-HT 1 did not fulfill this classification: 5-HT 1C . Therefore, with the approval of all scientists, 5-HT 1C was transferred to the 5-HT 2 family and renamed 5-HT2C (5).When this receptor was still called 5-HT 1C , receptor cloning was performed by the "functional cloning method" using Xenopus oocytes injected with an RNA library followed by electrophysiological detection. 13, 2014; Accepted October 13, 2014 Abstract. The serotonin 2C receptor subtype (5-HT2C) has a unique profession and continues to provide exciting and critical new information. The 5-HT2C is modulated at the RNA level by several mechanisms, including editing, short variant generation, and small RNAs. Recently, these phenomena, which had been demonstrated individually, were shown to be associated with each other. At present, many reports provide information about the influence of RNA regulation on receptor protein activities and expression, which was thought to be the final functional product. However, complicated behavior at the RNA stage allows us to imagine that the RNA itself has functional roles in the RNA universe. The 5-HT2C RNA may play several roles. This review will outline previous 5-HT2C studies and prospects for future studies.

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Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader–Willi syndrome

Cited by 118 publications

References 72 publications

Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease

Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease

5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists

Serotonin 2C Receptor as a Superhero: Diversities and Talents in the RNA Universe for Editing, Variant, Small RNA and Other Expected Functional RNAs

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