A number of autosomal dominant hereditary cerebral amyloid angiopathies are associated with defects in integral membrane protein 2B, ITM2B, including what are commonly known as familial British dementia (cerebral amyloid angiopathy, ITM2B-related, 1, FBhh0000249) and familial Danish dementia (cerebral amyloid angiopathy, ITM2B-related, 2, FBhh0000250). ITM2B (also known as BRI2) plays a role in the regulation of processing of the amyloid beta (A4) precursor protein (APP); APP is implicated in Alzheimer disease 1 (FBhh0000119). There is a single fly ortholog of ITM2B, CG3662, for which RNAi-targeting constructs and an allele caused by insertional mutagenesis have been generated. Dmel\CG3662 is also orthologous to human genes ITM2A and ITM2C.
Multiple UAS constructs of the human gene, Hsap\ITM2B, have been introduced into flies, including common disease-associated variants. Phenotypes are observed in the eye and other neural tissues; phenotypic differences between variants are detected. Variant(s) implicated in human disease tested (as transgenic human gene, ITM2B): the British variant form [*267R (+11aa)] and the Danish variant form (NM_021999. 4:c.786_795dupTTTAATTTGT ) have been introduced into flies. Both of these ITM2B mutations result in a carboxy extension of the protein.
The Drosophila CG3662 gene has not been genetically characterized.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Cerebral amyloid angiopathy (CAA), or cerebroarterial amyloidosis, refers to a pathologic process in which amyloid protein progressively deposits in cerebral blood vessel walls with subsequent degenerative vascular changes that usually result in spontaneous cerebral hemorrhage, recurrent headaches, ischemic lesions, hemorrhagic strokes, and progressive dementia (Revesz et al., 2003; pubmed: 14533778). [from MIM:605714; 2017.06.02]
Cerebral amyloid angiopathy (CAA) refers to the deposition of β-amyloid in the walls of the blood vessels of the central nervous system. It is a component of any disorder in which amyloid is deposited in the brain; it is not associated with systemic amyloidosis. While often asymptomatic, CAA may lead to dementia, intracranial hemorrhage, or transient neurologic events. [http://emedicine.medscape.com/article/1162720-overview, 2017.07.14]
ITM2B plays a regulatory role in the processing of the beta-amyloid A4 precursor protein (APP) and acts as an inhibitor of the beta-amyloid peptide aggregation and fibrils deposition. ITM2B encodes a transmembrane protein which is processed at the C-terminus by furin or furin-like proteases to produce a small secreted peptide which inhibits deposition of the β-amyloid peptide and its aggregation into toxic oligomers. [from Gene Cards, ITM2B; 2016.04.19]
Many to one: 3 human to 1 Drosophila; additional human orthologous genes are ITM2A and ITM2C.
