Senataxin (SETX) is an RNA-DNA helicase that mediates R-loop resolution, which is essential for the normal functioning of cells, including neurons. Setx mutations have been implicated in lower motor neuron diseases, such as amyotrophic lateral sclerosis type 4 (dominant mutations) and ataxia-oculomotor apraxia-2 (recessive mutations). Amyotrophic lateral sclerosis type 4 (ALS4) is an early-onset, autosomal dominant, disease characterized by very slow disease progression and sparing of the respiratory musculature (OMIM: 602433). Patients display limb weakness, severe muscle wasting, and pyramidal signs. One of the most common clinical mutations, L389S, may lead to a toxic gain-of-function resulting in motor neuron degeneration in ALS4. These Setx-L389S knock-in (KI) mice express the L389S clinical mutation. Heterozygous Setx-L389S KI mice are viable and fertile and demonstrate a mild neuromuscular phenotype. Homozygous mice are viable, but have not been fully evaluated by the donating laboratory (August 2023). Setx-L389S heterozygous mice display a significant increase in hind-limb clasping starting at 6 months of age, as well as decreased motor function determined by rotarod analysis, compared to wildtype controls. While there is little to no change in the number of motor neurons, ventral horn motor neurons from 13-month-old heterozygous Setx-L389S KI mice were significantly smaller in size compared to age-matched controls. Further, neuropathological characterization of these mice revealed nuclear clearing and cytosolic mislocalization of TDP-43 in ~10% of spinal cord motor neurons. These Setx-L389S KI mice may be useful for studying neurological diseases such as ALS4.

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Setx-L389S knock-in mice carry a leucine to serine substitution at position 389 (L389S) of the senataxin (Setx) gene. These mice may be useful for studying neurological diseases such as amyotrophic lateral sclerosis type 4 (ALS4) and ataxia-oculomotor apraxia-2 (AOA2).

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Our minimum guarantee for cryorecovery orders is 2 carriers. To ensure that your colony can be rapidly expanded upon arrival, additional carriers may be added to your order.