Acidified drinking water improves motor function, prevents tremors and changes disease trajectory in Cln2(R207X) mice, a model of late infantile Batten disease

Batten disease is a group of mostly pediatric neurodegenerative lysosomal storage disorders caused by mutations in the CLN1–14 genes. We have recently shown that acidified drinking water attenuated neuropathological changes and improved motor function in the Cln1(R151X) and Cln3(−/−) mouse models of infantile CLN1 and juvenile CLN3 diseases. Here we tested if acidified drinking water has beneficial effects in Cln2(R207X) mice, a nonsense mutant model of late infantile CLN2 disease. Cln2(R207X) mice have motor deficits, muscle weakness, develop tremors, and die prematurely between 4 and 6 months of age. Acidified water administered to Cln2(R207X) male mice from postnatal day 21 significantly improved motor function, restored muscle strength and prevented tremors as measured at 3 months of age. Acidified drinking water also changed disease trajectory, slightly delaying the death of Cln2(R207X) males and females. The gut microbiota compositions of Cln2(R207X) and wild-type male mice were markedly different and acidified drinking water significantly altered the gut microbiota of Cln2(R207X) mice. This suggests that gut bacteria might contribute to the beneficial effects of acidified drinking water. Our study demonstrates that drinking water is a major environmental factor that can alter disease phenotypes and disease progression in rodent disease models.