VAPB and ALS Sample Clauses

VAPB and ALS. ‌ A dominant missense mutation causing a proline to serine substitution at residue 56 in the VAPB gene was initially identified in eight Brazilian families with phenotypes ranging from typical ALS to late-onset SMA (Xxxxxxxxx et al., 2004). A further mutation causing a threonine to isoleucine change at position 46 has also been associated with ALS (Xxxx et al., 2010) (Figure 1.3). Interestingly, transgenic mice expressing VAPB P56S develop cytoplasmic TDP-43 accumulations in the spinal cord, but fail to develop overt motor neuron disease (Xxxxx et al., 2010). There are two VAP isoforms in mammals termed VAPA and VAPB that are encoded by different genes and which share approximately 63% sequence identity; both are expressed in most tissues and cell types including the nervous system (Amarilio et al., 2005; Xxxxxxx et al., 2008; Xxx et al., 2010a; Xxxxxxxxx et al., 1999; Xxxxxx et al., 2000; Xxxxxxx et al., 2007). VAPB comprises an N-terminal major sperm protein (MSP) domain, named for its similarity to the nematode MSP, a central coiled-coil domain and a C-terminal transmembrane domain which anchors it in the ER membrane (Xxxxxxxxx et al., 1999; Xxxxxx et al., 2000; Xxxxxxx et al., 1999) (Figure 1.3).