The mouse C9ORF72 ortholog is enriched in neurons known to degenerate in ALS and FTD

• DOI: 10.1038/nn.3566
• Publication Date: 2013-11-03T21:13:44Z
• Authors: Naoki Suzuki; Asif M Maroof; Florian T Merkle; Kathryn Koszka; Atsushi Intoh; Ian Armstrong; Rob Moccia; Brandi N Davis-Du...; Kevin Eggan
• Keywords: Male; 0301 basic medicine; Genotype; hippocampus; C9ORF72; 610; Mice, Transgenic; Nerve Tissue Proteins; Transfection; Article; Mice; 03 medical and health sciences; astrocyte; Animals; Guanine Nucleotide Exchange Factors; Humans; Amyotrophic lateral sclerosis (ALS); motor neuron; Cells, Cultured; Aged; Homeodomain Proteins; Neurons; microglial; C9orf72 Protein; Amyotrophic Lateral Sclerosis; frontotemporal dementia (FTD); cortical neuron; Brain; Nuclear Proteins; Proteins; Embryo, Mammalian; Repressor Proteins; Animals, Newborn; Gene Expression Regulation; Frontotemporal Dementia; Mutation; Acetylcholinesterase; Transcription Factors

Using transgenic mice harboring a targeted LacZ insertion, we studied the expression pattern of the C9ORF72 mouse ortholog (3110043O21Rik). Unlike most genes that are mutated in amyotrophic lateral sclerosis (ALS), which are ubiquitously expressed, the C9ORF72 ortholog was most highly transcribed in the neuronal populations that are sensitive to degeneration in ALS and frontotemporal dementia. Thus, our results provide a potential explanation for the cell type specificity of neuronal degeneration caused by C9ORF72 mutations.