Reference Report

Reference
Citation	Chai, A., Withers, J., Koh, Y.H., Parry, K., Bao, H., Zhang, B., Budnik, V., Pennetta, G. (2008). hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction. Hum. Mol. Genet. 17(2): 266--280. (Export to RIS)
FlyBase ID	FBrf0202930
Publication Type	Research paper
PubMed ID	17947296
PubMed Abstract	Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by selective death of motor neurons leading to spasticity, muscle wasting and paralysis. Human VAMP-associated protein B (hVAPB) is the causative gene of a clinically diverse group of MNDs including amyotrophic lateral sclerosis (ALS), atypical ALS and late-onset spinal muscular atrophy. The pathogenic mutation is inherited in a dominant manner. Drosophila VAMP-associated protein of 33 kDa A (DVAP-33A) is the structural homologue of hVAPB and regulates synaptic remodeling by affecting the size and number of boutons at neuromuscular junctions. Associated with these structural alterations are compensatory changes in the physiology and ultrastructure of synapses, which maintain evoked responses within normal boundaries. DVAP-33A and hVAPB are functionally interchangeable and transgenic expression of mutant DVAP-33A in neurons recapitulates major hallmarks of the human diseases including locomotion defects, neuronal death and aggregate formation. Aggregate accumulation is accompanied by a depletion of the endogenous protein from its normal localization. These findings pinpoint to a possible role of hVAPB in synaptic homeostasis and emphasize the relevance of our fly model in elucidating the patho-physiology underlying motor neuron degeneration in humans.
DOI	10.1093/hmg/ddm303
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Hum. Mol. Genet.
Title	Human Molecular Genetics
Publication Year	1992-
ISBN/ISSN	0964-6906
Data from Reference
Alleles (10)
	Hsap\VAPB^{P56S.Scer\UAS} Hsap\VAPB^Scer\UAS.cCa Scer\GAL4^C164 Scer\GAL4^D42 Scer\GAL4^elav-C155 Vap-33-1^{P58S.Scer\UAS} Vap-33-1^Scer\UAS.cPa Vap-33-1^Δ20 Vap-33-1^Δ166 Vap-33-1^Δ448
Constructs (4)
	P{UAS-DVAP-33A.P58S} P{UAS-Hsap\VAPB.C} P{UAS-Hsap\VAPB.P56S} P{UAS-Vap-33-1.P}
Genes (9)
	CG33523 fan GluRIIA GluRIIB GluRIIC GluRIID Hsap\VAPB Scer\GAL4 Vap-33-1
Insertions (3)
	P{GawB}C164 P{GawB}D42 P{GawB}elav^C155
Natural transposons (1)
	P-element