Comparative analysis of the gut microbiota composition in the Cln1R151X and Cln2R207X mouse models of Batten disease and in three wild-type mouse strains

Parker, Camille; Zhao, Jing; Pearce, David A.; Kovács, Attila

doi:10.1007/s00203-020-02007-6

Cited by 8 publications

(6 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the extent of the difference in the global gut microbiota composition (beta diversity) between 129S6/SvEv mice receiving H 2 SO 4 -acidified or non-acidified drinking water (Fig. 2 ) is similar to that we recently found between C57BL/6J and 129S6/SvEv mice, two very distinct mouse strains 39 . This magnitude of the H 2 SO 4 -acidified water-induced changes is beyond any possible interindividual variations in the gut microbiota among 129S6/SvEv mice.…”

Section: Discussionsupporting

confidence: 85%

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

Whipple

Agar

Zhao

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Acidification of drinking water to a pH between 2.5 and 3.0 is widely used to prevent the spread of bacterial diseases in animal colonies. Besides hydrochloric acid (HCl), sulfuric acid (H2SO4) is also used to acidify drinking water. Here we examined the effects of H2SO4-acidified drinking water (pH = 2.8) received from weaning (postnatal day 21) on the behavior and gut microflora of 129S6/SvEv mice, a mouse strain commonly used in transgenic studies. In contrast to HCl-acidified water, H2SO4-acidified water only temporarily impaired the pole-descending ability of mice (at 3 months of age), and did not change the performance in an accelerating rotarod test. As compared to 129S6/SvEv mice receiving non-acidified or HCl-acidified drinking water, the gut microbiota of 129S6/SvEv mice on H2SO4-acidified water displayed significant alterations at every taxonomic level especially at 6 months of age. Our results demonstrate that the effects of acidified drinking water on the behavior and gut microbiota of 129S6/SvEv mice depends on the acid used for acidification. To shed some light on how acidified drinking water affects the physiology of 129S6/SvEv mice, we analyzed the serum and fecal metabolomes and found remarkable, acidified water-induced alterations.

show abstract

Section: Discussionsupporting

confidence: 85%

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

Whipple

Agar

Zhao

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The gut microflora can significantly change in neurological and neurodegenerative diseases, and the changed microbiota, by its secreted metabolites and through the vagus nerve, affects immune cells and the central nervous system, contributing to disease development and pathology 18 . We have previously reported that the gut microbiota of 3-month-old Cln1 R151X mice is altered as compared to wild-type mice 19 . Here we showed that the gut microbiota was also significantly altered at 6 months of age (see Fig.…”

Section: Discussionmentioning

confidence: 94%

Acidified drinking water attenuates motor deficits and brain pathology in a mouse model of a childhood neurodegenerative disorder

Kovács

Gonzalez-Hernandez

Pearce

2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

We recently demonstrated that HCl-acidified drinking water, which is widely used in laboratory animal facilities, had some beneficial effects in the Cln3−/− mouse model of juvenile Batten disease, a neurodegenerative lysosomal storage disorder1. Here we tested if acidified drinking water has therapeutic effects in Cln1R151X nonsense mutant mice, a model of the infantile form of Batten disease. In Cln1R151X mice, acidified drinking water received from weaning prevented the impairment in pole climbing ability measured at 3 and 6 months of age. Histopathological analysis of the brain at 6 months showed that acidified drinking water decreased the amount of lysosomal storage material, reduced astrocytosis in the striatum and somatosensory barrelfield cortex, and attenuated microglial activation in the thalamus. Compared to wild-type mice, the gut microbiota of Cln1R151X mice was markedly different. Acidified drinking water significantly altered the gut microbiota composition of Cln1R151X mice, indicating a contribution of gut bacteria to the therapeutic effects of acidified water. Our results in Cln1R151X mice suggest that acidified drinking water may have beneficial effects for patients with infantile Batten disease. This study also verifies that acidified drinking water can modify disease phenotypes in mouse models, contributing to the inter-laboratory variations in neurological and pathological findings.

show abstract

“…Here, the HD treated sheep 1,164–15 died unexpectedly at 60.1 months of age from gastrointestinal stasis. Descriptions of constipation, abdominal pain and bloating, vomiting, gastric reflux, changes in gut microbiota, loss of enteric neurons and impaired gastrointestinal motility have been published and anecdotally reported for NCL patients and animal models ( Mole et al, 2021 ; Parker et al, 2021 ; Wang et al, 2021 ) so long-term future therapeutic strategies may be required for other pathologies, such as those in the enteric nervous system.…”

Section: Discussionmentioning

confidence: 99%

Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease

Mitchell,

Murray,

Wellby

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

CLN5 neuronal ceroid lipofuscinosis (NCL, Batten disease) is a rare, inherited fatal neurodegenerative disorder caused by mutations in the CLN5 gene. The disease is characterised by progressive neuronal loss, blindness, and premature death. There is no cure. This study evaluated the efficacy of intracerebroventricular (ICV) delivery of an adeno-associated viral vector encoding ovine CLN5 (scAAV9/oCLN5) in a naturally occurring sheep model of CLN5 disease. CLN5 affected (CLN5−/−) sheep received low, moderate, or high doses of scAAV9/oCLN5 at three disease stages. The treatment delayed disease progression, extended survival and slowed stereotypical brain atrophy in most animals. Of note, one high dose treated animal only developed mild disease symptomology and survived to 60.1 months of age, triple the natural life expectancy of an untreated CLN5−/− sheep. Eyesight was not preserved at any administration age or dosage. Histopathologic examination revealed that greater transduction efficiency was achieved through higher ICV doses, and this resulted in greater amelioration of disease pathology. Together with other pre-clinical data from CLN5−/− sheep, the safety and efficacy data from these investigational new drug (IND)-enabling studies supported the initiation of the first in-human CLN5 gene therapy clinical study using the ICV delivery route for the treatment of CLN5 NCL.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT05228145

show abstract

Comparative analysis of the gut microbiota composition in the Cln1R151X and Cln2R207X mouse models of Batten disease and in three wild-type mouse strains

Cited by 8 publications

References 60 publications

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

Acidified drinking water attenuates motor deficits and brain pathology in a mouse model of a childhood neurodegenerative disorder

Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease

Contact Info

Product

Resources

About