Dataset

DZNE-2025-00821

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset: Proteomics of brain from a myeloid specific NPC1 KO mouse

Müller, S. A.DZNE* ; Lichtenthaler, S.DZNE*

2024
PRoteomics IDEntifications Database

Abstract: Niemann-Pick type C (NPC) disease is an inherited lysosomal storage disorder mainly driven by mutations in NPC1 gene, causing lipid accumulation within late endosomes/lysosomes, and resulting in progressive neurodegeneration. Although microglial activation proceeds neuronal loss, it remains elusive whether loss of NPC1 in microglia actively contributes to NPC pathology. Here, we used a mouse model with depletion of NPC1 in myeloid cells to investigate the role of microglia in Niemann-Pick disease. In order to achieve the loss of NPC1 in myeloid cells, mice with floxed Npc1 alleles (Npc1 flox/flox) were crossed with mice expressing the constitutively active Cre recombinase under the myeloid-specific promotor of Cx3cr1. Hyperactive microglia initiated a pathological cascade resembling NPC-like phenotypes, including shortened lifespan, motor impairments, astrogliosis, neuroaxonal pathology and increased levels of neuronal injury biomarker NF-L. To study the differential vulnerability between the brain regions, we compared the cerebellar with the cerebral (brain without cerebellum) proteome in Cre- and Cre+ mice at late pathological stages. Our results suggest that microglial loss of NPC1 has profound effects on brain cell homeostasis especially in the cerebrum.

---

Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

---

---

Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article Dinkel, L. (First author)DZNE* ; Hummel, S.Extern* ; Zenatti, V.DZNE* ; Malara, M.DZNE* ; Tillmann, Y.DZNE* ; Colombo, A. V.DZNE* ; Sebastian Monasor, L.DZNE* ; Suh, J. H. ; Logan, T. ; Roth, S. ; Paeger, L.DZNE* ; Hoffelner, P. ; Bludau, O. ; Schmidt, A.DZNE* ; Müller, S. A.DZNE* ; Schifferer, M.DZNE* ; Nuscher, B. ; Njavro, J. R.DZNE* ; Prestel, M.DZNE* ; Bartos, L. M. ; Wind-Mark, K.DZNE* ; Slemann, L. ; Hoermann, L. ; Kunte, S. T. ; Gnoerich, J.Extern* ; Lindner, S. ; Simons, M.DZNE* ; Herms, J.DZNE* ; Paquet, D. ; Lichtenthaler, S. F.DZNE* ; Bartenstein, P. ; Franzmeier, N. ; Liesz, A. ; Grosche, A. ; Bremova-Ertl, T. ; Catarino, C. ; Beblo, S. ; Bergner, C. ; Schneider, S. A. ; Strupp, M. ; Di Paolo, G. ; Brendel, M.DZNE* ; Tahirovic, S. (Last author)DZNE*
Myeloid cell-specific loss of NPC1 in mice recapitulates microgliosis and neurodegeneration in patients with Niemann-Pick type C disease.
Science translational medicine 16(776), eadl4616 (2024) [10.1126/scitranslmed.adl4616]2024   Files BibTeX | EndNote: XML, Text | RIS

---