Project description:Background: Activation of stress pathways intrinsic to the β cell are thought to both accelerate β cell death and increase β cell immunogenicity in type 1 diabetes (T1D). However, information on the timing and scope of these responses is lacking. Methods: To identify temporal and disease-related changes in islet β cell protein expression, SWATH-MS/MS proteomics analysis was performed on islets collected longitudinally from NOD mice and NOD-SCID mice rendered diabetic through T cell adoptive transfer. Findings: In islets collected from female NOD mice at 10, 12, and 14 weeks of age, we found a time-restricted upregulation of proteins involved in the maintenance of β cell function and stress mitigation, followed by loss of expression of protective proteins that heralded diabetes onset. Pathway analysis identified EIF2 signaling and the unfolded protein response, mTOR signaling, mitochondrial function, and oxidative phosphorylation as commonly modulated pathways in both diabetic NOD mice and NOD-SCID mice rendered acutely diabetic by adoptive transfer, highlighting this core set of pathways in T1D pathogenesis. In immunofluorescence validation studies, β cell expression of protein disulfide isomerase A1 (PDIA1) and 14-3-3b were found to be increased during disease progression in NOD islets, while PDIA1 plasma levels were increased in pre-diabetic NOD mice and in the serum of children with recent-onset T1D compared to age and sex-matched non-diabetic controls. Interpretation: We identified a common and core set of modulated pathways across distinct mouse models of T1D and identified PDIA1 as a potential human biomarker of β cell stress in T1D.
Project description:Prior to the onset of autoimmune destruction, type 1 diabetic patients and an animal model thereof, the nonobese diabetic (NOD) mouse, show morphological and functional abnormalities in target organs, which may act as inciting events for leukocyte infiltration. To better understand these abnormalities, but without the complications associated with inflammatory infiltrates, we examined genes expressed in autoimmune target tissues (pancreas, submandibular glands, and lacrimal glands) of NOD/scid mice and of autoimmune-resistant C57BL6/scid mice. Experiment Overall Design: Pancreata (6 weeks old mice), submandibular (9 and 15 weeks), and lacrimal glands (15 weeks) from individual NOD-scid and B6-scid mice were isolated for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Protein source in diet greatly influences the incidence of type-1 diabetes (T1D) in non-obese diabetic (NOD) mouse colonies. NOD mice fed a diet containing hydrolyzed casein (HC) as the sole protein source are protected from T1D. Exposure to HC also reduced beta-cell insulin secretion during glucose challenge suggesting that beneficial changes to beta-cell physiology might protect NOD mice from T1D. We used single cell RNA sequencing (scRNAseq) to contrast the transcriptional profiles of beta-cells and from the pancreatic islets of Langerhans of NOD mice with the scid mutation (scid mice were used to avoid confouding influence of infiltrating leukocytes) fed a 20% HC diet or a standard chow diet.
2023-01-04 | GSE217495 | GEO
Project description:NOD mice gut bacteria with/out acetic treatment
Project description:Glioblastoma cell lines were xenografted onto mice and resulting tumors were profiled by microarray. Xenograft recipient mice were NOD/SCID/gamma (NSG) male mice 3 months old.
2013-07-01 | GSE46028 | GEO
Project description:Germ free NOD mice gut bacteria treated with TID bacteria
