Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model
Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurogenetic disorders caused by mutations in 14 different genes. CLN6 disease manifests as variant late-infantile NCL (vLINCL) or as an adult variant. In childhood, symptoms include speech delay, vision loss, cognitive and mot...
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2025-04-01
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| author | Victoria Chaoul Sara Saab Omar Shmoury Ramy Alam Lynn Al Aridi Nadine J. Makhoul Jihane Soueid Rose-Mary Boustany |
| author_facet | Victoria Chaoul Sara Saab Omar Shmoury Ramy Alam Lynn Al Aridi Nadine J. Makhoul Jihane Soueid Rose-Mary Boustany |
| author_sort | Victoria Chaoul |
| collection | DOAJ |
| description | Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurogenetic disorders caused by mutations in 14 different genes. CLN6 disease manifests as variant late-infantile NCL (vLINCL) or as an adult variant. In childhood, symptoms include speech delay, vision loss, cognitive and motor decline, seizures, and early death. An in-depth characterization of a naturally occurring Cln6 mutant mouse (<i>Cln6<sup>nclf</sup></i>) is presented, with implications for translational research. The expanded phenotype provides data showing early death, vision loss, and motor deficits in male and female <i>Cln6<sup>nclf</sup></i> mice. Diminished visual acuity in <i>Cln6<sup>nclf</sup></i> mice was noted at 28 weeks of age, but the pathological loss of retinal layers began as early as 2 weeks or postnatal day 14 (P14). Apoptosis was confirmed by TUNEL staining in the <i>Cln6<sup>nclf</sup></i> mouse brain at P8 and in the retina at P12. A peak in glial fibrillary acidic protein (GFAP) expression was established as a normal developmental phenomenon in the wild-type and <i>Cln6<sup>nclf</sup></i> mouse brain cerebellum and the CA2–CA3 regions of the hippocampus at P8. In <i>Cln6<sup>nclf</sup></i> mice, GFAP levels were elevated at P12 in the cerebellum and hippocampus. In the retina, a developmental peak in gliosis was absent, with increased astrogliosis noted at P6 and P8 in female and male <i>Cln6<sup>nclf</sup></i> mice, respectively. This highlights the lack of a sex-dependent response in wild-type mice. These novel data position the <i>Cln6<sup>nclf</sup></i> mouse model as a useful tool for screening potential therapeutics for human CLN6 disease. |
| format | Article |
| id | doaj-art-e9aaa282078b4294bd3603873b9e17ae |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-e9aaa282078b4294bd3603873b9e17ae2025-08-20T03:52:58ZengMDPI AGCells2073-44092025-04-0114966110.3390/cells14090661Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse ModelVictoria Chaoul0Sara Saab1Omar Shmoury2Ramy Alam3Lynn Al Aridi4Nadine J. Makhoul5Jihane Soueid6Rose-Mary Boustany7Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, American Unibersity of Beirut, Beirut 1107 2020, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut 1107 2020, LebanonNeuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurogenetic disorders caused by mutations in 14 different genes. CLN6 disease manifests as variant late-infantile NCL (vLINCL) or as an adult variant. In childhood, symptoms include speech delay, vision loss, cognitive and motor decline, seizures, and early death. An in-depth characterization of a naturally occurring Cln6 mutant mouse (<i>Cln6<sup>nclf</sup></i>) is presented, with implications for translational research. The expanded phenotype provides data showing early death, vision loss, and motor deficits in male and female <i>Cln6<sup>nclf</sup></i> mice. Diminished visual acuity in <i>Cln6<sup>nclf</sup></i> mice was noted at 28 weeks of age, but the pathological loss of retinal layers began as early as 2 weeks or postnatal day 14 (P14). Apoptosis was confirmed by TUNEL staining in the <i>Cln6<sup>nclf</sup></i> mouse brain at P8 and in the retina at P12. A peak in glial fibrillary acidic protein (GFAP) expression was established as a normal developmental phenomenon in the wild-type and <i>Cln6<sup>nclf</sup></i> mouse brain cerebellum and the CA2–CA3 regions of the hippocampus at P8. In <i>Cln6<sup>nclf</sup></i> mice, GFAP levels were elevated at P12 in the cerebellum and hippocampus. In the retina, a developmental peak in gliosis was absent, with increased astrogliosis noted at P6 and P8 in female and male <i>Cln6<sup>nclf</sup></i> mice, respectively. This highlights the lack of a sex-dependent response in wild-type mice. These novel data position the <i>Cln6<sup>nclf</sup></i> mouse model as a useful tool for screening potential therapeutics for human CLN6 disease.https://www.mdpi.com/2073-4409/14/9/661CLN6 disease<i>Cln6<sup>nclf</sup></i> miceapoptosisneurodegenerationmotor deficitsvision loss |
| spellingShingle | Victoria Chaoul Sara Saab Omar Shmoury Ramy Alam Lynn Al Aridi Nadine J. Makhoul Jihane Soueid Rose-Mary Boustany Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model Cells CLN6 disease <i>Cln6<sup>nclf</sup></i> mice apoptosis neurodegeneration motor deficits vision loss |
| title | Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model |
| title_full | Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model |
| title_fullStr | Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model |
| title_full_unstemmed | Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model |
| title_short | Expanded Phenotype of the <i>Cln6<sup>nclf</sup></i> Mouse Model |
| title_sort | expanded phenotype of the i cln6 sup nclf sup i mouse model |
| topic | CLN6 disease <i>Cln6<sup>nclf</sup></i> mice apoptosis neurodegeneration motor deficits vision loss |
| url | https://www.mdpi.com/2073-4409/14/9/661 |
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