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Characterization of the visceral and neuronal phenotype of 4L/PS-NA mice modeling Gaucher disease

Schiffer, Victoria, Santiago-Mujika, Estibaliz, Flunkert, Stefanie, Schmidt, Staffan, Farcher, Martina, Loeffler, Tina, Schilcher, Irene, Posch, Maria, Neddens, Joerg, Sun, Ying, Kehr, Jan, Hutter-Paier, Birgit·2020·PLOS ONE
DOI 10.1371/journal.pone.0227077PMC PMC6957154
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Fig 1 General health and motor deficits of 4L/PS-NA mice over age. Eight, 12 and 18 week old 4L/PS-NA mice and control littermates were analyzed for body weight (A), the hanging time in seconds in the wire suspension test (B), the total number of slips (C) and the active time in the beam walk test (D), the latency to fall off the rotating rod of the Rota Rod test (E) and the number of bites per episode in the pasta gnawing test (F). Two-way ANOVA followed by Bonferroni’s post hoc test. n = 7 per group. Mean ± SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001.
Fig 1 General health and motor deficits of 4L/PS-NA mice over age. Eight, 12 and 18 week old 4L/PS-NA mice and control littermates were analyzed for body weight (A), the hanging time in seconds in the wire suspension test (B), the total number of slips (C) and the active time in the beam walk test (D), the latency to fall off the rotating rod of the Rota Rod test (E) and the number of bites per episode in the pasta gnawing test (F). Two-way ANOVA followed by Bonferroni’s post hoc test. n = 7 per group. Mean ± SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001.CC BY · PubMed Central
Fig 2 Tissue weight of 4L/PS-NA mice over age. Tissue weight of liver (A), lung (B), spleen (C), thymus (D), cerebellum (left hemisphere, E) and left brain hemisphere without cerebellum (F) were measured at 5, 12, or 18 week of age. Two-way ANOVA followed by Bonferroni’s post hoc test. 4L/PS-NA: 5 weeks: n = 6; 12 weeks: n = 7; 18 weeks: n = 15; Control: 5 weeks: n = 5; 12 weeks: n = 7; 18 weeks: n = 16; Mean + SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001.
Fig 2 Tissue weight of 4L/PS-NA mice over age. Tissue weight of liver (A), lung (B), spleen (C), thymus (D), cerebellum (left hemisphere, E) and left brain hemisphere without cerebellum (F) were measured at 5, 12, or 18 week of age. Two-way ANOVA followed by Bonferroni’s post hoc test. 4L/PS-NA: 5 weeks: n = 6; 12 weeks: n = 7; 18 weeks: n = 15; Control: 5 weeks: n = 5; 12 weeks: n = 7; 18 weeks: n = 16; Mean + SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001.CC BY · PubMed Central
Fig 3 Enlarged leukocytes in visceral organs of 4L/PS-NA mice. The liver (A), lung (B), spleen (C) and thymus (D) of 4L/PS-NA mice and control littermates were labeled with CD45 antibody at the age of 5, 12 and 18 weeks; green: CD45; blue: DAPI. Scale bars: Overview: 100 μm, inserts: 10 μm.
Fig 3 Enlarged leukocytes in visceral organs of 4L/PS-NA mice. The liver (A), lung (B), spleen (C) and thymus (D) of 4L/PS-NA mice and control littermates were labeled with CD45 antibody at the age of 5, 12 and 18 weeks; green: CD45; blue: DAPI. Scale bars: Overview: 100 μm, inserts: 10 μm.CC BY · PubMed Central
Fig 4 Enlarged macrophages in visceral organs of 4L/PS-NA mice. The liver (A), lung (B), spleen (C) and thymus (D) of 4L/PS-NA mice and control littermates were labeled with F4/80 antibody at the age of 5, 12 and 18 weeks; green: F4/80; blue: DAPI. Scale bars: Overview: 100 μm, inserts: 10 μm. Arrows indicate enlarged macrophages surrounding alveoles.
Fig 4 Enlarged macrophages in visceral organs of 4L/PS-NA mice. The liver (A), lung (B), spleen (C) and thymus (D) of 4L/PS-NA mice and control littermates were labeled with F4/80 antibody at the age of 5, 12 and 18 weeks; green: F4/80; blue: DAPI. Scale bars: Overview: 100 μm, inserts: 10 μm. Arrows indicate enlarged macrophages surrounding alveoles.CC BY · PubMed Central
Fig 5 Quantification of glucocerebrosidase, glucosylceramide and glucosylsphingosine in 4L/PS-NA mice over age. The cortex of 5, 12 and 18 week old 4L/PS-NA mice, control animals as well as C57Bl/6 mice was analyzed for glucocerebrosidase activity by 4-MUG assay (A). Whole brain homogenates of 5, 12 and 18 week old 4L/PS-NA mice, control animals as well as C57Bl/6 mice were analyzed for glucosylceramide (B) and glucosylsphingosine (C) levels in μg/g wet weight (B) or ng/g wet weight (C). Two-way ANOVA followed by Bonferroni’s post hoc test. Values of C57Bl/6 mice (triangles in B and C) were excluded from all statistical analyses; n = 5 for 4L/PS-NA and control animals; n = 3 for C57Bl/6 mice. Mean + SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001.
Fig 5 Quantification of glucocerebrosidase, glucosylceramide and glucosylsphingosine in 4L/PS-NA mice over age. The cortex of 5, 12 and 18 week old 4L/PS-NA mice, control animals as well as C57Bl/6 mice was analyzed for glucocerebrosidase activity by 4-MUG assay (A). Whole brain homogenates of 5, 12 and 18 week old 4L/PS-NA mice, control animals as well as C57Bl/6 mice were analyzed for glucosylceramide (B) and glucosylsphingosine (C) levels in μg/g wet weight (B) or ng/g wet weight (C). Two-way ANOVA followed by Bonferroni’s post hoc test. Values of C57Bl/6 mice (triangles in B and C) were excluded from all statistical analyses; n = 5 for 4L/PS-NA and control animals; n = 3 for C57Bl/6 mice. Mean + SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001.CC BY · PubMed Central
Fig 6 Quantification of astrocytosis and activated microglia in 4L/PS-NA mice over age. The cortex (A,C) and hippocampus (B,D) of 4L/PS-NA mice was analyzed for GFAP (A,B) and IBA1 (C,D) immunoreactive area (IR) in percent at the age of 5, 12 and 18 weeks compared to control littermates. Two-way ANOVA followed by Bonferroni’s post hoc test. n = 5 per group. Mean + SEM. *differences between genotypes; #differences between age groups; **p<0.01; ***p<0.001. E: Representative images of GFAP, IBA1 and DAPI labeling of the hippocampal CA1 region in 18 week old 4L/PS-NA and control mice. Scale bar: 50 μm.
Fig 6 Quantification of astrocytosis and activated microglia in 4L/PS-NA mice over age. The cortex (A,C) and hippocampus (B,D) of 4L/PS-NA mice was analyzed for GFAP (A,B) and IBA1 (C,D) immunoreactive area (IR) in percent at the age of 5, 12 and 18 weeks compared to control littermates. Two-way ANOVA followed by Bonferroni’s post hoc test. n = 5 per group. Mean + SEM. *differences between genotypes; #differences between age groups; **p<0.01; ***p<0.001. E: Representative images of GFAP, IBA1 and DAPI labeling of the hippocampal CA1 region in 18 week old 4L/PS-NA and control mice. Scale bar: 50 μm.CC BY · PubMed Central
Fig 7 Quantification of α-synuclein and calbindin in 4L/PS-NA mice over age. The cerebellum (A,C) and hippocampus (B,D) of 4L/PS-NA mice was analyzed for pan α-synuclein (A,B) and calbindin (C,D) immunoreactive area (IR) in percent at the age of 5, 12 and 18 weeks compared to control littermates. Two-way ANOVA followed by Bonferroni’s post hoc test. n = 5 per group. Mean + SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001. E: Representative images of pan α-synuclein, calbindin and DAPI labeling of the hippocampal CA1 region in 5 week old 4L/PS-NA and control mice. Scale bar: 50 μm.
Fig 7 Quantification of α-synuclein and calbindin in 4L/PS-NA mice over age. The cerebellum (A,C) and hippocampus (B,D) of 4L/PS-NA mice was analyzed for pan α-synuclein (A,B) and calbindin (C,D) immunoreactive area (IR) in percent at the age of 5, 12 and 18 weeks compared to control littermates. Two-way ANOVA followed by Bonferroni’s post hoc test. n = 5 per group. Mean + SEM. *differences between genotypes; #differences between age groups; *p<0.05; **p<0.01; ***p<0.001. E: Representative images of pan α-synuclein, calbindin and DAPI labeling of the hippocampal CA1 region in 5 week old 4L/PS-NA and control mice. Scale bar: 50 μm.CC BY · PubMed Central
Fig 8 Pathological alterations in the cerebellum of 4L/PS-NA mice. The cerebellum of 18 week old 4L/PS-NA mice (B) and control littermates (A) were labeled with antibodies against α-synuclein (red) and calbindin (green) and nuclei were visualized with DAPI (blue). Scale bar: 1,000 μm. 1, 2, 3 and 4 show magnifications of areas indicated in the overview images. DAPI staining is not shown in higher magnification images. arrow: Purkinje cell axon; ML: molecular layer; PCL: Purkinje cell layer; GCL: granule cell layer; WM: white matter.
Fig 8 Pathological alterations in the cerebellum of 4L/PS-NA mice. The cerebellum of 18 week old 4L/PS-NA mice (B) and control littermates (A) were labeled with antibodies against α-synuclein (red) and calbindin (green) and nuclei were visualized with DAPI (blue). Scale bar: 1,000 μm. 1, 2, 3 and 4 show magnifications of areas indicated in the overview images. DAPI staining is not shown in higher magnification images. arrow: Purkinje cell axon; ML: molecular layer; PCL: Purkinje cell layer; GCL: granule cell layer; WM: white matter.CC BY · PubMed Central

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Research works printed but not linked: 48

  1. E Sidransky, 2009, Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease, The New England journal of medicine, 361, 1651, 10.1056/NEJMoa0901281 · DOI · Paper page
  2. O Goker-Alpan, 2010, Glucocerebrosidase is present in alpha-synuclein inclusions in Lewy body disorders, Acta neuropathologica, 120, 641, 10.1007/s00401-010-0741-7 · DOI
  3. J Stirnemann, 2017, A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments, International journal of molecular sciences, 18, 10.3390/ijms18020441 · DOI
  4. K Weiss, 2015, The clinical management of Type 2 Gaucher disease, Molecular genetics and metabolism, 114, 110, 10.1016/j.ymgme.2014.11.008 · DOI
  5. Y Sun, 2002, Prosaposin: threshold rescue and analysis of the "neuritogenic" region in transgenic mice, Molecular genetics and metabolism, 76, 271, 10.1016/S1096-7192(02)00114-2 · DOI
  6. N Fujita, 1996, Targeted disruption of the mouse sphingolipid activator protein gene: a complex phenotype, including severe leukodystrophy and wide-spread storage of multiple sphingolipids, Human molecular genetics, 5, 711, 10.1093/hmg/5.6.711 · DOI
  7. VL Tybulewicz, 1992, Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene, Nature, 357, 407, 10.1038/357407a0 · DOI
  8. E Sidransky, 1992, Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene, Pediatric research, 32, 494, 10.1203/00006450-199210000-00023 · DOI
  9. Y Liu, 1998, Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure, Proceedings of the National Academy of Sciences of the United States of America, 95, 2503, 10.1073/pnas.95.5.2503 · DOI
  10. YH Xu, 2003, Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease, The American journal of pathology, 163, 2093, 10.1016/S0002-9440(10)63566-3 · DOI · Paper page
  11. Y Sun, 2005, Gaucher disease mouse models: point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants, Journal of lipid research, 46, 2102, 10.1194/jlr.M500202-JLR200 · DOI · Paper page
  12. A Rolfs, 2013, Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients, PloS one, 8, e79732, 10.1371/journal.pone.0079732 · DOI
  13. YH Xu, 2011, Accumulation and distribution of alpha-synuclein and ubiquitin in the CNS of Gaucher disease mouse models, Molecular genetics and metabolism, 102, 436, 10.1016/j.ymgme.2010.12.014 · DOI
  14. R Rabl, 2016, Quantitative evaluation of orofacial motor function in mice: The pasta gnawing test, a voluntary and stress-free behavior test, Journal of neuroscience methods, 274, 125, 10.1016/j.jneumeth.2016.10.006 · DOI
  15. R Rabl, 2017, Early start of progressive motor deficits in Line 61 alpha-synuclein transgenic mice, BMC neuroscience, 18, 22, 10.1186/s12868-017-0341-8 · DOI
  16. K Wong, 2004, Neuropathology provides clues to the pathophysiology of Gaucher disease, Molecular genetics and metabolism, 82, 192, 10.1016/j.ymgme.2004.04.011 · DOI
  17. MA Verity, 1977, Infantile Gaucher's disease: neuropathology, acid hydrolase activities and negative staining observations, Neuropadiatrie, 8, 89, 10.1055/s-0028-1091508 · DOI
  18. YH Xu, 2014, Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice, Human molecular genetics, 23, 3943, 10.1093/hmg/ddu105 · DOI
  19. JH Choi, 2011, Aggregation of alpha-synuclein in brain samples from subjects with glucocerebrosidase mutations, Molecular genetics and metabolism, 104, 185, 10.1016/j.ymgme.2011.06.008 · DOI
  20. JR Mazzulli, 2011, Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies, Cell, 146, 37, 10.1016/j.cell.2011.06.001 · DOI · Paper page
  21. M Abdelwahab, 2017, Previously unrecognized behavioral phenotype in Gaucher disease type 3, Neurology Genetics, 3, e158, 10.1212/NXG.0000000000000158 · DOI
  22. A Tylki-Szymanska, 2010, Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry, Journal of inherited metabolic disease, 33, 339, 10.1007/s10545-009-9009-6 · DOI
  23. A Tajima, 2009, Clinical and genetic study of Japanese patients with type 3 Gaucher disease, Molecular genetics and metabolism, 97, 272, 10.1016/j.ymgme.2009.05.001 · DOI
  24. P Sorrentino, 2016, Impaired gait kinematics in type 1 Gaucher's Disease, Journal of Parkinson's disease, 6, 191, 10.3233/JPD-150660 · DOI
  25. M Abdelwahab, 2016, Long-term follow-up and sudden unexpected death in Gaucher disease type 3 in Egypt, Neurology Genetics, 2, e55, 10.1212/NXG.0000000000000055 · DOI
  26. J Charrow, 2000, The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease, Archives of internal medicine, 160, 2835, 10.1001/archinte.160.18.2835 · DOI
  27. G Amir, 1999, Pulmonary pathology in Gaucher's disease, Hum Pathol, 30, 666, 10.1016/S0046-8177(99)90092-8 · DOI
  28. M Nishino, 2006, he thymus: a comprehensive review, TRadiographics: a review publication of the Radiological Society of North America, Inc, 26, 335, 10.1148/rg.262045213 · DOI
  29. Y Sun, 2010, Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits, Human molecular genetics, 19, 1088, 10.1093/hmg/ddp580 · DOI
  30. R Hamler, 2017, Glucosylceramide and Glucosylsphingosine Quantitation by Liquid Chromatography-Tandem Mass Spectrometry to Enable In Vivo Preclinical Studies of Neuronopathic Gaucher Disease, Analytical chemistry, 89, 8288, 10.1021/acs.analchem.7b01442 · DOI
  31. EE Jones, 2017, Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry, SLAS discovery: advancing life sciences R & D, 22, 1218, 10.1177/2472555217719372 · DOI
  32. M Fuller, 2015, Rapid, single-phase extraction of glucosylsphingosine from plasma: A universal screening and monitoring tool, Clinica chimica acta; international journal of clinical chemistry, 450, 6, 10.1016/j.cca.2015.07.026 · DOI
  33. V Murugesan, 2016, Glucosylsphingosine is a key biomarker of Gaucher disease, American journal of hematology, 91, 1082, 10.1002/ajh.24491 · DOI
  34. TA Burrow, 2015, CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11 years of therapy: clinical, histopathologic, and biochemical findings, Molecular genetics and metabolism, 114, 233, 10.1016/j.ymgme.2014.08.011 · DOI
  35. EB Vitner, 2012, Contribution of brain inflammation to neuronal cell death in neuronopathic forms of Gaucher's disease, Brain: a journal of neurology, 135, 1724, 10.1093/brain/aws095 · DOI · Paper page
  36. T Farfel-Becker, 2011, Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease, Human molecular genetics, 20, 1375, 10.1093/hmg/ddr019 · DOI
  37. EI Ginns, 2014, Neuroinflammation and alpha-synuclein accumulation in response to glucocerebrosidase deficiency are accompanied by synaptic dysfunction, Molecular genetics and metabolism, 111, 152, 10.1016/j.ymgme.2013.12.003 · DOI
  38. C Ran, 2016, Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden, Neurobiology of aging, 45, 212 e5, 10.1016/j.neurobiolaging.2016.04.022 · DOI
  39. Y Li, 2015, Gaucher-Associated Parkinsonism, Cellular and molecular neurobiology, 35, 755, 10.1007/s10571-015-0176-8 · DOI
  40. L Vilageliu, 2017, Involvement of Gaucher Disease Mutations in Parkinson Disease, Curr Protein Pept Sci, 18, 758, 10.2174/1389203717666160311115956 · DOI
  41. G Maor, 2019, The effect of mutant GBA1 on accumulation and aggregation of alpha-synuclein, Human molecular genetics
  42. YV Taguchi, 2017, Glucosylsphingosine Promotes alpha-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease. The Journal of neuroscience: the official journal of the, Society for Neuroscience, 37, 9617
  43. V Cullen, 2011, Acid beta-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter alpha-synuclein processing, Annals of neurology, 69, 940, 10.1002/ana.22400 · DOI
  44. T Pampols, 1999, Neuronopathic juvenile glucosylceramidosis due to sap-C deficiency: clinical course, neuropathology and brain lipid composition in this Gaucher disease variant, Acta neuropathologica, 97, 91, 10.1007/s004010050960 · DOI
  45. N Conradi, 1991, Late-infantile Gaucher disease in a child with myoclonus and bulbar signs: neuropathological and neurochemical findings, Acta neuropathologica, 82, 152, 10.1007/BF00293959 · DOI
  46. A Yoneshige, 2010, A mutation in the saposin C domain of the sphingolipid activator protein (Prosaposin) gene causes neurodegenerative disease in mice, Journal of neuroscience research, 88, 2118, 10.1002/jnr.22371 · DOI
  47. Y Sun, 2010, Specific saposin C deficiency: CNS impairment and acid beta-glucosidase effects in the mouse, Human molecular genetics, 19, 634, 10.1093/hmg/ddp531 · DOI
  48. H Mizukami, 2002, Systemic inflammation in glucocerebrosidase-deficient mice with minimal glucosylceramide storage, The Journal of clinical investigation, 109, 1215, 10.1172/JCI0214530 · DOI

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Metadata

Authors
Schiffer, V., Santiago-Mujika, E., Flunkert, S., Schmidt, S., Farcher, M., Loeffler, T., Schilcher, I., Posch, M., Neddens, J., Sun, Y., Kehr, J., & Hutter-Paier, B.
ORCID
Flunkert, Stefanie
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2020-01-13
Volume
15
Issue
1
Pages
e0227077
ISSN
1932-6203
DOI
10.1371/journal.pone.0227077
PMC
PMC6957154
Cited by
11
References
0
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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Schiffer, V., Santiago-Mujika, E., Flunkert, S., Schmidt, S., Farcher, M., Loeffler, T., Schilcher, I., Posch, M., Neddens, J., Sun, Y., Kehr, J., & Hutter-Paier, B. (2020). Characterization of the visceral and neuronal phenotype of 4L/PS-NA mice modeling Gaucher disease. PLOS ONE. https://doi.org/10.1371/journal.pone.0227077