The Swiss Spinal Cord Injury Cohort Study (SwiSCI) biobank: from concept to reality.

OBJECTIVES To describe the concept, establishment and the operationalization of the biobank of the Swiss Spinal Cord Injury Cohort Study (SwiSCI), the available biosamples, and demographic and clinical characteristics of study participants. SETTING The SwiSCI biobank is a platform for research within SwiSCI. It collects and processes serum, plasma, PBMCs, RNA, DNA, and urine from three rehabilitation centers. Samples are collected at admission to first rehabilitation and at discharge. Additionly, the biobank provides services to projects nested in SwiSCI or otherclinical trials among Spinal Cord Injury population. METHODS Descriptive statistics were used for an overview of available biosamples, study participant characteristics, and comparison of the participating centers. RESULTS Between the SwiSCI biobank establishment on June 27th, 2016, and October 19th, 2023, the SwiSCI Study has obtained informed consent from 524 individuals. Of these, 315 (60.1%) have agreed to donate biospecimens to the biobank. The average age of the contributors was 54 years (range: 38-65), with the majority being male (80%). Most participants suffered from traumatic injuries (66%) and were classified as paraplegic (64%). Approximately 80% presented with motor and sensory-incomplete SCI. The median Spinal Cord Independence Measure (SCIM) score was 31 (Interquartile Range: 19-58). The proportion of individuals providing paired biosamples at two distinct time points ranged from 63% (for RNA) to 65% (for urine and urine sediment). CONCLUSIONS The SwiSCI biobank is a unique platform designed to serve as a basis for collaborative SCI research, including multi-omics approaches. The longitudinal collection of biospecimens and cryopreservation of multiple aliquots for each participant are fundamental for scrutinizing the temporal associations, ensuring research reproducibility, and achieving an adequate sample size for future investigations

MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy

Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients

Generation of <i>Mto1</i> knockdown mice by gene trap mutagenesis.

<p>(A) Integration of gene trap vector U3CEO in intron 6 of <i>Mto1</i>. Arrows indicate amplificons for RT-PCR. (B) RT-PCR of heart tissue shows reduced levels of <i>Mto1</i> transcripts using primers covering sequences 5′ or 3′ to the integration site, ***p<0.001. (C) Western blot showing a clear reduction of MTO1 protein in <i>Mto1</i>−/− mouse embryonic fibroblasts as compared to <i>Mto1</i>+/+ controls.</p

Heart weight related to body weight was significantly increased in <i>Mto1</i>−/− mutant mice as compared to controls, both in 5 months old mice (n = 15, *p<0.05) and as a trend in 10 months old mice (n = 8, n.s.).

<p>Heart weight related to body weight was significantly increased in <i>Mto1</i>−/− mutant mice as compared to controls, both in 5 months old mice (n = 15, *p<0.05) and as a trend in 10 months old mice (n = 8, n.s.).</p

ECG parameters (Data are presented as mean +/− standard error of mean).

<p>ECG parameters (Data are presented as mean +/− standard error of mean).</p

Behavioral analysis of <i>Mto1</i> mutant mice using a modified holeboard.

<p><i>Mto1</i>−/−mice show increased horizontal locomotor activity (A) as well as increased mean velocity (B) as compared to controls. Anxiety-related behavior measured via the time on board (C) and group contact (D) was also significantly changed; object exploration was increased (E) and acoustic startle response decreased (F), *p<0.05; **p<0.01.</p