TDP43 was originally identified as a protein which binds to the “transactivation response” (TAR) sequence found in the long terminal repeat of the HIV-1 virus genome (1). UV cross-linking of HeLa cell extract revealed a 43kDa protein which was cloned and sequenced and shown to contain a two central copies of the ~90 amino acid RNA recognition motif or RRM domain. RRM is an acronym for RNA Recognition Motif, and this domain is found in many proteins which bind single stranded RNA and some which bind single stranded DNA. It also has a single bipartite nuclear localization sequence in the N-terminus region in front of the first RRM domain, and the C-terminal region, beyond the second RRM domain is rich in glycine, asparagine and glutamine. TDP43 is normally expressed in the mammalian CNS but accumulates in nuclear inclusions in the neurons of patients with frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other pathologies (2-4). Disease related point mutations in TDP43 are almost always found in the C-terminal region. TDP43 is related in protein sequence to FUS/TLS, EWSR1 and TAF15 and all four proteins have a tendency, especially when mutated, to aggregate into inclusions and are implicated in a variety of neurological disorders (5,6).The MCA-3H8 antibody was made against full length recombinant human protein and works well on western blots and on histological sections, staining FTLD and ALS related inclusion bodies, see “Additional Info” tab. It has also been shown to identify inclusions seen in Alzheimer’s disease (4). We have shown that MCA-3H8 reacts with TDP43 from human, cow, pig, mouse, rat and other mammals and that the epitope is in the center the peptide HNSNRQLERSGRFGGNPGGF, amino acids 264-283, C-terminal to second RRM domain of the human sequence. This is the region typically in TDP43 inclusions (see here). This peptide is 100% conserved in a wide variety of mammalian species so it is likely that the antibody is effective on many other species also. The KD for this antibody in 1.16 X 10^-9M. The antibody is also an excellent marker of nuclei in cell fractionation experiments. Mouse select image at left for rather view, and on “additional info” tab for more information.