Biology subjects

Wakenight, P.

Publications and source records attributed to Wakenight, P..

3 recordsLinked to original sources

bioRxiv2024

The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet {beta}-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (IFIH1), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1A946T) and confers an increased risk for several autoimmune diseases, including T1D. We hypothesized that the IFIH1A946T risk variant, (IFIH1R) would promote T1D pathogenesis by stimulating type I interferon (IFN I) signaling leading to immune cell alterations. To test this, we developed Ifih1R knock-in mice on the non-obese diabetic (NOD) mouse background, a spontaneous T1D model. Our results revealed a modest increase in diabetes incidence and insulitis in Ifih1R compared to non-risk Ifih1 (Ifih1NR) mice and a significant acceleration of diabetes onset in Ifih1R females. Ifih1R mice exhibited a significantly enhanced interferon stimulated gene (ISG) signature compared to Ifih1NR, indicative of increased IFN I signaling. Ifih1R mice exhibited an increased frequency of plasma cells as well as tissue-dependent changes in the frequency and activation of CD8+ T cells. Our results indicate that IFIH1R may contribute to T1D pathogenesis by altering the frequency and activation of immune cells. These findings advance our knowledge on the connection between the rs1990760 variant and T1D. Further, these data are the first to demonstrate effects of Ifih1R in NOD mice, which will be important to consider for the development of therapeutics for T1D.

immunology↗

bioRxiv2023

Chromosome-scale genome assembly of the African spiny mouse (Acomys cahirinus)

There is increasing interest in the African spiny mouse (Acomys cahirinus) as a model organism because of its ability for regeneration of tissue after injury in skin, muscle, and internal organs such as the kidneys. A high-quality reference genome is needed to better understand these regenerative properties at the molecular level. Here, we present an improved reference genome for A. cahirinus generated from long Nanopore sequencing reads. We confirm the quality of our annotations using RNA sequencing data from four different tissues. Our genome is of higher contiguity and quality than previously reported genomes from this species and will facilitate ongoing efforts to better understand the regenerative properties of this organism.

genomics↗

bioRxiv2018

Scarless repair of acute and chronic kidney injury in African Spiny mice (Acomys cahirinus)

Solid organ fibrosis is a major burden on global health and medical care costs. Muroid rodents of the genus Acomys (African Spiny mice) are terrestrial mammals that evolved remarkable abilities to regenerate severe skin wounds without scar formation. However, whether scar-free wound repair in Acomys extends beyond skin to vital internal organs is not known. Here, we used two aggressive kidney injury models known to produce severe renal fibrosis and show that despite equivalent acute kidney injury, there was rapid restoration of nephron structure and function without fibrosis in Acomys compared to extensive fibrosis leading to renal failure in Mus musculus. These results suggest Acomys species have evolved genomic adaptations for wound healing that activate regenerative repair pathways not only in skin, but also in vital internal organs. Our findings have important implications for discovering a long-sought evolutionary solution to internal organ injury and regeneration.

pathology↗