Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila

Lanikea B King; Marta Koch; Keith R Murphy; Yoheilly Velazquez; William W Ja; Seth M Tomchik

doi:10.1534/g3.115.026484

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Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila

Journal article

Open access

Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila

Lanikea B King, Marta Koch, Keith R Murphy, Yoheilly Velazquez, William W Ja and Seth M Tomchik

G3 : genes - genomes - genetics, Vol.6(4), pp.1083-1093

04/07/2016

DOI: 10.1534/g3.115.026484

PMCID: PMC4825643

PMID: 26896440

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Abstract

Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits.

Animals

Drosophila - physiology

Drosophila Proteins - genetics

Drosophila Proteins - metabolism

Genetic Association Studies

Grooming

Male

Mutation

Neurofibromin 1 - genetics

Neurofibromin 1 - metabolism

Photoperiod

Sleep

Details

Title: Subtitle: Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila
Creators: Lanikea B King - Scripps Research Institute
Marta Koch - Scripps Research Institute
Keith R Murphy - Scripps Research Institute
Yoheilly Velazquez - Scripps Research Institute
William W Ja - Scripps Research Institute
Seth M Tomchik - Scripps Research Institute
Resource Type: Journal article
Publication Details: G3 : genes - genomes - genetics, Vol.6(4), pp.1083-1093
DOI: 10.1534/g3.115.026484
PMID: 26896440
PMCID: PMC4825643
NLM abbreviation: G3 (Bethesda)
ISSN: 2160-1836
eISSN: 2160-1836
Grant note: R00 MH092294 / NIMH NIH HHS R25 GM096955 / NIGMS NIH HHS R01 AG045036 / NIA NIH HHS
Language: English
Date published: 04/07/2016
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984303742602771

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