Initially identified in an analysis of two genome-wide association studies (FBrf0223922), the human gene CELF1 is proposed as a candidate susceptibility locus for Alzheimer disease. CELF1 encodes an RNA-binding protein implicated in the regulation of several post-transcriptional events. There are two orthologous genes in Drosophila, bru1 and bru2. Classical amorphic and hypomorphic alleles have been generated for bru1; RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for both bru1 and bru2. There is a second paralogous gene in human, CELF2.
In Drosophila, several investigations of the role of CELF1 in the process of tau-associated pathologies (which include Alzheimer disease; see FBhh0000101) have been carried out, using expression of either the wild-type human gene (Hsap\MAPT) or variants of Hsap\MAPT implicated in neurological disease (see FBhh0000111). Expression of wild-type or variants of Hsap\MAPT in the Drosophila eye results in rough-eye and reduced-size phenotypes.
The human Hsap\CELF1 gene has been introduced into flies; expression of this gene in the Drosophila eye also results in a rough eye phenotype. Co-expression of Hsap\CELF1 and Hsap\MAPT in the Drosophila eye significantly enhances the phenotypes observed for either gene alone.
When Dmel\bru2 is co-expressed with Hsap\MAPT in the eye, partial rescue of the Hsap\MAPT toxicity phenotype is observed. RNAi-mediated reduction in the expression of bru1 enhances the eye phenotypes associated with tau toxicity; overexpression in the eye reduces the tau toxicity phenotype. Loss-of-function alleles of bru1 are typically female sterile and exhibit defects in indirect flight muscles. Physical and genetic interactions of Dmel\bru1 have been characterized; see below and in the gene report for bru1.
[updated Apr. 2020 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Locus identified as showing significant association with susceptibility to Alzheimer disease in an analysis of two genome-wide association studies (GWAS).
CELF1 is associated with late-onset Alzheimer disease in a GWAS study (see GWAS Catalog, below in 'External links').
CELF1 encodes an RNA-binding protein implicated in the regulation of several post-transcriptional events, including pre-mRNA alternative splicing, mRNA translation and stability. [from Gene Cards, CELF1; 2016.06.02]
Many to many: 2 human to 2 Drosophila; additional high-scoring human ortholog is CELF2.
Higher-scoring Drosophila ortholog of human genes CELF1 and CELF2 (2 Drosophila to 2 human). Dmel\bru1 shares 46-49% identity and 57-62% similarity with the human genes.
Moderate-scoring ortholog of human CELF1 and CELF2 (2 Drosophila to 2 human). Dmel\bru2 shares 42% identity and 52-53% similarity with the human genes.
