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Publication
Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis
Syndrome.
Authors Huang WH, Guenthner CJ, Xu J, Nguyen T, Schwarz LA, Wilkinson AW, Gozani O,
Chang HY, Shamloo M, Luo L
Submitted By Submitted Externally on 1/3/2017
Status Published
Journal Neuron
Year 2016
Date Published
Volume : Pages 92 : 392 - 406
PubMed Reference 27693255
Abstract Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis
syndrome (SMS), which is associated with diverse neurodevelopmental and
behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein but
little is known about its molecular function or the cell types responsible for
SMS symptoms. Using genetically engineered mice, we found that Rai1
preferentially occupies DNA regions near active promoters and promotes the
expression of a group of genes involved in circuit assembly and neuronal
communication. Behavioral analyses demonstrated that pan-neural loss of
Rai1 causes deficits in motor function, learning, and food intake. These
SMS-like phenotypes are produced by loss of Rai1 function in distinct neuronal
types: Rai1 loss in inhibitory neurons or subcortical glutamatergic neurons
causes learning deficits, while Rai1 loss in Sim1(+) or SF1(+) cells causes
obesity. By integrating molecular and organismal analyses, our study suggests
potential therapeutic avenues for a complex neurodevelopmental disorder.




Strains
StrainDevelopment StatusCreation MethodOptions
B6;129-Rai1tm1Luo Tg(Sim1-cre)1LowlPhenotyping ongoingknockin
View
B6;129-Rai1tm1Luo Tg(Nr5a1-cre)7LowlPhenotyping ongoingknockin
View
B6.129-Rai1tm1LuoNot Applicableknockin
View




Genes
SymbolDescription
Nr5a1nuclear receptor subfamily 5, group A, member 1
Sim1single-minded 1
Rai1retinoic acid induced 1

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