Juvenile neuronal ceroid lipofuscinosis (JNCL) is an inherited neurodegenerative disease caused by mutations in the gene encoding CLN3 lysosomal protein. Contrary to late-infantile neuronal ceroid lipofuscinosis (LINCL), caused by mutations in the lysosomal protein tripeptidyl peptidase 1 (TPP1), no animal models or effective treatment exist for JNCL. Previous research characterized mouse models with either mutated Tpp1 or Cln3, but the phenotype of a double Cln3/Tpp1 mutant, as well as the function of CLN3 protein, remain unclear.

Researchers from Huidagene Therapeutics Co. Ltd. have evaluated the effects of adenine base editing (ABE)-induced exon skipping of exon 50 in a humanized mouse model of Duchenne muscular dystrophy (DMD).

MicroRNA-184 (miR-184) mutations have been previously tied to inherited anterior segment dysgenesis, potentially causing cataracts and keratoconus. To elucidate the involvement of miR-184 in ocular disorders, Chinese researchers have developed a miR-184 knockout zebrafish model. Investigators used CRISPR-Cas9 technology to delete two miR-184 paralogs (dre-mir-184-1 and dre-mir-184-2) in zebrafish, which are highly conserved between human and fly.

Murine models are primarily used in Alzheimer’s disease (AD) research, but differences between rodents and primates may prevent a true understanding of the mechanisms of the disease.

Chimeric antigen receptor (CAR) T-cell therapy is a powerful approach for patients with hematologic malignancies, such as leukemia. Its broad use may be associated with life-threatening toxicities such as neurotoxicity and cytokine release syndrome (CRS).

Geleophysic dysplasia (GD) is an autosomal recessive disease characterized by facial features, short stature, limited joint mobility and cardiovascular and respiratory abnormalities, which can lead to a significant mortality rate. The disease is caused by biallelic genetic variants in the ADAMTSL2 gene. Little is known about the pathogenesis of the disease, but dysregulation of the TGF-β pathway has been shown to be involved.

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of several neurological disorders, such as multiple sclerosis (MS). Its transmembrane form activates the type II tumor necrosis factor receptor (TNFR2), functioning via cell-to-cell contact. In contrast, its soluble form activates TNFR1; studies in animal models have evidenced TNFR1 to activate neurotoxic pathways, while TNFR2 activation pathways may have protective effects within the central nervous system due to activation of reparative mechanisms.