Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a type of motor neuron disease. Motor neuron diseases are a group of chronic and progressive degenerative neurological disorders with unclear etiologies, selectively affecting spinal anterior horn cells, brainstem motor neurons, cortical pyramidal cells, and the corticospinal and corticobulbar tracts. Motor neuron diseases encompass four clinical types: ALS, progressive muscular atrophy, progressive bulbar palsy, and primary lateral sclerosis, with ALS being the most common among them.

The known causative genes for ALS include SOD1, TDP-43, and FUS. In both ALS and frontotemporal lobar degeneration (FTLD), the key pathological change involves the accumulation of pathogenic TDP-43 in the cytoplasm, leading to the formation of cytoplasmic inclusions.Due to the substantial similarities between pigs and humans, the use of transgenic pigs to study the pathological changes caused by mutant polyglutamine proteins has led to the identification of unique pathologies not observed in small animal models.

Pig Breed: Tibetan Pig

1.Mutant TDP-43 was found to be distributed in the cytoplasm of brain tissue of transgenic pigs, and this phenomenon was also seen in the brains of patients.

2.By studying the interaction of TDP-43 with PSF and its associated RNA splicing function, we provide new evidence for the species-dependent cytoplasmic distribution of mutant TDP-43 and gained new insights into how cytoplasmic accumulation of TDP-43 mutants can lead to abnormal gene expression.

3.It is enlightening to identify the pathological pathways and protein interactions involved in ALS and FTLD, and is helpful for the research of targeted treatment options.