Tracking sex-dependent differences in a mouse model of CLN6-Batten disease
Abstract Background CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-019-0994-8 |
| _version_ | 1811220992132907008 |
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| author | McKayla J. Poppens Jacob T. Cain Tyler B. Johnson Katherine A. White Samantha S. Davis Rachel Laufmann Alexander D. Kloth Jill M. Weimer |
| author_facet | McKayla J. Poppens Jacob T. Cain Tyler B. Johnson Katherine A. White Samantha S. Davis Rachel Laufmann Alexander D. Kloth Jill M. Weimer |
| author_sort | McKayla J. Poppens |
| collection | DOAJ |
| description | Abstract Background CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death occurring in the second decade of life. In this study, we investigate whether sex differences in a mouse model of CLN6-Batten disease impact disease onset and progression. Results A number of noteworthy differences were observed including elevated accumulation of mitochondrial ATP synthase subunit C in the thalamus and cortex of female Cln6 mutant mice at 2 months of age. Moreover, female mutant mice showed more severe behavioral deficits. Beginning at 9 months of age, female mice demonstrated learning and memory deficits and suffered a more severe decline in motor coordination. Further, compared to their male counterparts, female animals succumbed to the disease at a slightly younger age, indicating an accelerated disease progression. Conversely, males showed a marked increase in microglial activation at 6 months of age in the cortex relative to females. Conclusions Thus, as female Cln6 mutant mice exhibit cellular and behavioral deficits that precede similar pathologies in male mutant mice, our findings suggest the need for consideration of sex-based differences in CLN6 disease progression during development of preclinical and clinical studies. |
| first_indexed | 2024-04-12T07:52:23Z |
| format | Article |
| id | doaj.art-7b28cbfe339a47748e8ffc5fdc88fd71 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-12T07:52:23Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-7b28cbfe339a47748e8ffc5fdc88fd712022-12-22T03:41:34ZengBMCOrphanet Journal of Rare Diseases1750-11722019-01-011411710.1186/s13023-019-0994-8Tracking sex-dependent differences in a mouse model of CLN6-Batten diseaseMcKayla J. Poppens0Jacob T. Cain1Tyler B. Johnson2Katherine A. White3Samantha S. Davis4Rachel Laufmann5Alexander D. Kloth6Jill M. Weimer7Pediatrics and Rare Diseases Group, Sanford ResearchPediatrics and Rare Diseases Group, Sanford ResearchPediatrics and Rare Diseases Group, Sanford ResearchPediatrics and Rare Diseases Group, Sanford ResearchPediatrics and Rare Diseases Group, Sanford ResearchPediatrics and Rare Diseases Group, Sanford ResearchDepartment of Biology, Augustana UniversityPediatrics and Rare Diseases Group, Sanford ResearchAbstract Background CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death occurring in the second decade of life. In this study, we investigate whether sex differences in a mouse model of CLN6-Batten disease impact disease onset and progression. Results A number of noteworthy differences were observed including elevated accumulation of mitochondrial ATP synthase subunit C in the thalamus and cortex of female Cln6 mutant mice at 2 months of age. Moreover, female mutant mice showed more severe behavioral deficits. Beginning at 9 months of age, female mice demonstrated learning and memory deficits and suffered a more severe decline in motor coordination. Further, compared to their male counterparts, female animals succumbed to the disease at a slightly younger age, indicating an accelerated disease progression. Conversely, males showed a marked increase in microglial activation at 6 months of age in the cortex relative to females. Conclusions Thus, as female Cln6 mutant mice exhibit cellular and behavioral deficits that precede similar pathologies in male mutant mice, our findings suggest the need for consideration of sex-based differences in CLN6 disease progression during development of preclinical and clinical studies.http://link.springer.com/article/10.1186/s13023-019-0994-8Neuronal ceroid lipofuscinosesRare diseaseLysosomal storage disorderNeurodegenerative diseasePediatric disease |
| spellingShingle | McKayla J. Poppens Jacob T. Cain Tyler B. Johnson Katherine A. White Samantha S. Davis Rachel Laufmann Alexander D. Kloth Jill M. Weimer Tracking sex-dependent differences in a mouse model of CLN6-Batten disease Orphanet Journal of Rare Diseases Neuronal ceroid lipofuscinoses Rare disease Lysosomal storage disorder Neurodegenerative disease Pediatric disease |
| title | Tracking sex-dependent differences in a mouse model of CLN6-Batten disease |
| title_full | Tracking sex-dependent differences in a mouse model of CLN6-Batten disease |
| title_fullStr | Tracking sex-dependent differences in a mouse model of CLN6-Batten disease |
| title_full_unstemmed | Tracking sex-dependent differences in a mouse model of CLN6-Batten disease |
| title_short | Tracking sex-dependent differences in a mouse model of CLN6-Batten disease |
| title_sort | tracking sex dependent differences in a mouse model of cln6 batten disease |
| topic | Neuronal ceroid lipofuscinoses Rare disease Lysosomal storage disorder Neurodegenerative disease Pediatric disease |
| url | http://link.springer.com/article/10.1186/s13023-019-0994-8 |
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