Optineurin deficiency induces patchy hair loss but it is not sufficient to cause amyotrophic lateral sclerosis in mice

Moharir, Shivranjani C; Swarup, Ghanshyam

doi:10.1016/j.bbadis.2022.166470

Cited by 3 publications

(11 citation statements)

References 34 publications

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“…It is of note though that detailed immune cell characterization performed in C9ORF72 -/mouse model showed a higher CD86 expression in splenic cDCs in 5-month-old mice (42), which is in line with results in two-year-old Optn 470T mice. In conclusion, we found no evidence of advanced immunosenescence and/or inflammageing in the Optn 470T model and unlike the previous report in blood (22), we found an expected CD4 + /CD8 + T cell ratio in spleens at both one and two years of age.…”

Section: Discussioncontrasting

confidence: 99%

“…It is of note though that the above-mentioned Optn D477N mouse model, which, unlike the lentiviral OPTN E478G model, expresses physiological levels of ubiquitin-binding optineurin mutation, did not exhibit overt ALS symptoms up to one year of age, although no detailed neurological or neuropathological analysis was reported (17). Overall, we can conclude that similar to previously published Optn -/- models (23,38,21,22), ageing up to two years was insufficient to elicit ALS/FTD phenotype in a ubiquitin-binding-deficient Optn 470T mouse model.…”

Section: Discussionsupporting

confidence: 86%

“…Overall, we can conclude that similar to previously published Optn -/models (23,38,21,22), ageing up to two years was insufficient to elicit ALS/FTD phenotype in a ubiquitin-bindingdeficient Optn 470T mouse model.…”

Section: Discussionsupporting

confidence: 85%

“…Notably, in both males and females, we failed to find differences in motor (rotarod and wire-hanging) and cognitive (novel object recognition and passive avoidance) tests between WT and Optn 470T mice, suggesting that optineurin insufficiency was unable to induce an ALS/FTD-like phenotype. Therefore, these results showed that Optn 470T mice were similar to optineurin-deficient Optn -/- mice made by several individual groups, which also showed no obvious neurological phenotype during ageing (23,38,21,22), except for a mildly decreased frequency of hind leg usage reported by Ito et al (15). The latter report also showed spinal cord dysmyelination, which was contested in a follow-up study (38).…”

Section: Discussionsupporting

confidence: 68%

“…One report detected slight motor deficits (in vertical rearing activity) and dysmyelination in the spinal cords of optineurin deficient (Optn -/-) mice at three months of age, with no further phenotype exacerbation up to two years, and no motor neuron loss (15). However, motor deficits were not detected in two other Optn -/mouse models (21,22), despite TDP-43 aggregation and diminished numbers of spinal cord neurons detected in one of the studies (21). Notably, no signs of neuroinflammation or protein aggregation were observed in one-year-old mice with CNS-specific optineurin knock-out (23).…”

Section: Introductionmentioning

confidence: 99%

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Neuroimmune characterization of optineurin insufficiency mouse model during ageing

Prtenjača

Peradinović

Markovinović

et al. 2023

Preprint

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Optineurin is a multifunctional polyubiquitin-binding protein implicated in inflammatory signalling. Optineurin mutations are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), neurodegenerative diseases characterised by neuronal loss, neuroinflammation, and peripheral immune disbalance. However, the pathogenic role of optineurin mutations is unclear. We previously observed no phenotype in the unmanipulated young optineurin insufficiency mice (Optn470T), designed to mimic ALS/FTD-linked truncations deficient in polyubiquitin binding. The purpose of this study was to investigate whether ageing would trigger neurodegeneration. We performed a neuroimmune characterization of ageing wild-type (WT) and Optn470T mice. No motor or cognitive differences were detected between the genotypes. Neuropathological analyses demonstrated signs of ageing including lipofuscin accumulation and microglial activation. However, this was not worsened in Optn470T mice, and they did not exhibit TAR DNA-binding protein 43 (TDP-43) aggregation or neuronal loss. Spleen immunophenotyping uncovered T cell immunosenescence at two years but without notable differences between the WT and Optn470T mice. Conventional dendritic cells (cDC) and macrophages exhibited increased expression of activation markers in two-year-old Optn470T males but not females, although the numbers of innate immune cells were similar between genotypes. Altogether, a combination of optineurin insufficiency and ageing did not induce ALS/FTD-like neuropathology in mice.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neuroimmune characterization of optineurin insufficiency mouse model during ageing

Prtenjača

Peradinović

Markovinović

et al. 2023

Preprint

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Molecular aspects of cytoprotection by Optineurin during stress and disease

Swarup,

Medchalmi,

Ramachandran

et al. 2025

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Neuroimmune characterization of optineurin insufficiency mouse model during ageing

Prtenjača¹,

Peradinović²,

Markovinović³

et al. 2023

Sci Rep

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Optineurin is a multifunctional polyubiquitin-binding protein implicated in inflammatory signalling. Optineurin mutations are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), neurodegenerative diseases characterised by neuronal loss, neuroinflammation, and peripheral immune disbalance. However, the pathogenic role of optineurin mutations is unclear. We previously observed no phenotype in the unmanipulated young optineurin insufficiency mice (Optn470T), designed to mimic ALS/FTD-linked truncations deficient in polyubiquitin binding. The purpose of this study was to investigate whether ageing would trigger neurodegeneration. We performed a neurological, neuropathological, and immunological characterization of ageing wild-type (WT) and Optn470T mice. No motor or cognitive differences were detected between the genotypes. Neuropathological analyses demonstrated signs of ageing including lipofuscin accumulation and microglial activation in WT mice. However, this was not worsened in Optn470T mice, and they did not exhibit TAR DNA-binding protein 43 (TDP-43) aggregation or neuronal loss. Spleen immunophenotyping uncovered T cell immunosenescence at two years but without notable differences between the WT and Optn470T mice. Conventional dendritic cells (cDC) and macrophages exhibited increased expression of activation markers in two-year-old Optn470T males but not females, although the numbers of innate immune cells were similar between genotypes. Altogether, a combination of optineurin insufficiency and ageing did not induce ALS/FTD-like immune imbalance and neuropathology in mice.

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Optineurin deficiency induces patchy hair loss but it is not sufficient to cause amyotrophic lateral sclerosis in mice

Cited by 3 publications

References 34 publications

Neuroimmune characterization of optineurin insufficiency mouse model during ageing

Neuroimmune characterization of optineurin insufficiency mouse model during ageing

Molecular aspects of cytoprotection by Optineurin during stress and disease

Neuroimmune characterization of optineurin insufficiency mouse model during ageing

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