Effect of primary copper metabolism disturbance on elemental, protein, and lipid composition of the organs in Jackson toxic milk mouse.
Copper metabolism
Neurodegeneration
Neurofilament
Toxic milk mouse
Wilson’s disease
Journal
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
ISSN: 1572-8773
Titre abrégé: Biometals
Pays: Netherlands
ID NLM: 9208478
Informations de publication
Date de publication:
04 Oct 2024
04 Oct 2024
Historique:
received:
17
07
2024
accepted:
19
09
2024
medline:
4
10
2024
pubmed:
4
10
2024
entrez:
4
10
2024
Statut:
aheadofprint
Résumé
Toxic milk (txJ) is an autosomal recessive mutation in the Atp7b gene in the C3H/HeJ strain, observed at The Jackson Laboratory in Maine, USA. TxJ mice exhibit symptoms similar to those of human Wilson's disease (WD). The study aimed to verify organ involvement in a mouse model of WD. TxJ mice and control animals were sacrificed at 2, 4, 8, and 14 months of age. Total X-ray Fluorescence Spectroscopy (TXRF) was used to determine the elemental concentration in organs. Tissue chemical composition was measured by Fourier Transform Infrared Spectroscopy (FTIR). Additionally, hybrid mapping of FTIR and microXRF was performed. Elevated concentrations of Cu were observed in the liver, striatum, eye, heart, and duodenum of txJ mice across age groups. In the striatum of the oldest txJ mice, there was lower lipid content and a higher fraction of saturated fats. The secondary structure of striatum proteins was disturbed in txJ mice. In the livers of txJ mice, higher concentrations of saturated fats and disturbances in the secondary structure of proteins were observed. The concentration of neurofilaments was significantly higher in txJ serum. The distribution of Cu deposits in brains was uniform with no prevalence in any anatomic structure in either group, but significant protein structure changes were observed exclusively in the striatum of txJ. In this txJ animal model of WD, pathologic copper accumulation occurs in the duodenum, heart, and eye tissues. Increased copper concentration in the liver and brain results in increased saturated fat content and disturbances in secondary protein structure, leading to hepatic injury and neurodegeneration.
Identifiants
pubmed: 39365499
doi: 10.1007/s10534-024-00640-y
pii: 10.1007/s10534-024-00640-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
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