Tor1a-flox Mouse

TOR1A, also known as TorsinA, is a gene involved in the endoplasmic reticulum stress response pathway [4]. Variants in this gene are associated with various neurological disorders, highlighting its significance in normal neurological function [1,2,3,6,7,8,9]. Mouse models, especially gene knockout (KO) and conditional knockout (CKO) models, have been crucial in studying TOR1A's function [5].

In a Tor1a CKO mouse model where the gene was knocked out in the spinal cord and dorsal root ganglia (DRG), mice developed early-onset generalized torsional dystonia, recapitulating the human condition. This showed that spinal neural circuit dysfunction, especially affecting motor neurons, is a key pathophysiological substrate of DYT1-TOR1A dystonia [5]. Additionally, excess Lipin enzyme activity was found in human DYT-TOR1A dystonia patient cells and in Tor1a mouse models, and reducing Lpin1 in these models improved survival and suppressed neurodegeneration, motor dysfunction, and nuclear membrane pathology, suggesting abnormal phosphatidic acid metabolism in TOR1A-related diseases [9].

In conclusion, TOR1A plays a vital role in normal neurological function, particularly in motor control through spinal neural circuits. Mouse models have been instrumental in revealing its role in DYT-TOR1A dystonia and related diseases, and in identifying potential therapeutic targets such as Lipin enzyme activity [5,9].