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Using Model Organisms to Study Complex Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 4322

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Dipartimento di Biologia e Biotecnologie, Istituto di Biologia e Patologia Molecolari del Consiglio Nazionale delle Ricerche (IBPM-CNR), Università Sapienza di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy
Interests: chromatin structure and function; heterochromatin; drosophila melanogaster; mitosis and male meiosis; cytokinesis; DNA repair; cancer epigenetics
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Special Issue Information

Dear Colleagues,

A model organism is a living species that allows for the study of specific biological problems, and the discoveries may be applied—with a limited number of adjustments—to a wide range of other species. To be defined as a “model”, an organism should also possess additional properties, such as being relatively simple, having the possibility to be established in a number of laboratories, having rapid generation times and a relatively low rearing cost, having stable and easy to recognize phenotypes, allowing to be studied at the “-omics” level, and having the availability of specific tool to study the modification of gene expression, to perform loss- and gain-of-function experiments. Classical model organisms include both prokaryotes (the bacterium Escherichia coli) and eukaryotes, either unicellular (the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe, or the numerous human cell cultures used worldwide, especially in cancer research) or multicellular, such as the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the zebrafish Danio rerio, the plant Arabidopsis thaliana, the African clawed frog Xenopus laevis, the rat Rattus norvegicus and the mouse Mus musculus. Additional models were developed over time, which are also quite distant from each other on an evolutionary scale to overcome the limitations of working on a simplified model, as correctly noted by Bertile and coworkers in a recent paper (https://doi.org/10.1038/s42003-023-05458-x).

The main aim of studying model organisms is, in most instances, to have a better understanding of human pathologies and unveil potential therapeutic targets. The conservation of basic cellular functions, such as DNA replication and repair, transcription and translation, post-transcriptional regulation, epigenetics and physiology, in fact makes these organisms amenable for studying human disease.

The aim of this Special Issue is to collect the most up-to-date research showing the use of model organisms to study human conditions. We welcome the submission of original research and review articles in this field, either using classical and non-classical models, as well as all contributions which provide novel insights into how models have contributed to our understanding of the etiology of and therapeutic approaches to human pathology.

Dr. Roberto Piergentili
Guest Editor

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Keywords

  • model organism
  • Escherichia coli
  • yeast
  • Caenorhabditis elegans
  • Drosophila melanogaster
  • zebrafish
  • Arabidopsis thaliana
  • Xenopus laevis
  • rat and mouse model
  • human disease
  • inherited disease
  • cancer
  • rare disease
  • genetics
 

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Published Papers (4 papers)

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Research

15 pages, 2018 KiB  
Article
Rat Model of Endogenous and Exogenous Hyperammonaemia Induced by Different Diets
by Janine Donaldson, Tomasz Jacek, Piotr Wychowański, Kamil Zaworski, Dominika Szkopek, Jarosław Woliński, Danica Grujic, Stefan Pierzynowski and Kateryna Pierzynowska
Int. J. Mol. Sci. 2025, 26(5), 1818; https://doi.org/10.3390/ijms26051818 - 20 Feb 2025
Viewed by 379
Abstract
Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant [...] Read more.
Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats, resulting in the development of endogenous HA, while the MAD diet caused moderate changes in liver metabolism, resulting in the development of exogenous HA. Interestingly, the commonly used oral treatments Lactulose and Rifaximin did not ameliorate hyperammonaemia during or after the treatment period. In conclusion, even though the diets used in the current study caused somewhat similar hyperammonaemia, they seemed to provoke different metabolic consequences. The latter can have an impact on the severity of the resulting hyperammonaemia and thus on the hyperammonaemia-induced encephalopathy, resulting in the development of distinguishing cognitive and metabolic (liver) effects compared to other forms of encephalopathy. We hypothesized that these rat models, with significantly increased serum ammonia levels, along with different liver injuries, could serve as a suitable double animal model for the testing of new, oral enzyme therapies for hepatic encephalopathy in future studies. Full article
(This article belongs to the Special Issue Using Model Organisms to Study Complex Human Diseases)
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11 pages, 2078 KiB  
Communication
The Diurnal Variation in Mitochondrial Gene in Human Type 2 Diabetic Mesenchymal Stem Cell Grafts
by Michiko Horiguchi, Kenichi Yoshihara, Yoichi Mizukami, Kenji Watanabe, Yuya Tsurudome and Kentaro Ushijima
Int. J. Mol. Sci. 2025, 26(2), 719; https://doi.org/10.3390/ijms26020719 - 16 Jan 2025
Viewed by 802
Abstract
The application of regenerative therapy through stem cell transplantation has emerged as a promising avenue for the treatment of diabetes mellitus (DM). Transplanted tissue homeostasis is affected by disturbances in the clock genes of stem cells. The aim of this study is to [...] Read more.
The application of regenerative therapy through stem cell transplantation has emerged as a promising avenue for the treatment of diabetes mellitus (DM). Transplanted tissue homeostasis is affected by disturbances in the clock genes of stem cells. The aim of this study is to investigate the diurnal variation in mitochondrial genes and function after transplantation of adipose-derived mesenchymal stem cells (T2DM-ADSCs) from type 2 diabetic patients into immunodeficient mice. Diurnal variation in mitochondrial genes was assessed by next-generation sequencing. As a result, the diurnal variation in mitochondrial genes showing troughs at ZT10 and ZT22 was observed in the group transplanted with adipose-derived mesenchymal stem cells derived from healthy individuals (N-ADSC). On the other hand, in the group transplanted with T2DM-ADSCs, diurnal variation indicative of troughs was observed at ZT18, with a large phase and amplitude deviation between the two groups. To evaluate the diurnal variation in mitochondrial function, we quantified mitochondrial DNA copy number using the Human mtDNA Monitoring Primer Set, measured mitochondrial membrane potential using JC-1, and evaluated mitophagy staining. The results showed a diurnal variation in mitochondrial DNA copy number, mitophagy, mitochondrial membrane potential, and NF-kB signaling in the N-ADSC transplant group. In contrast, no diurnal variation was observed in T2DM-ADSC transplants. The diurnal variation in mitochondrial function revealed in this study may be a new marker for the efficiency of T2DM-ADSC transplantation. Full article
(This article belongs to the Special Issue Using Model Organisms to Study Complex Human Diseases)
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12 pages, 3053 KiB  
Communication
Circadian Rhythms of Clock Genes After Transplantation of Mesenchymal Stem Cells with Type 2 Diabetes Mellitus
by Michiko Horiguchi, Kenichi Yoshihara, Kenji Watanabe, Yuya Tsurudome, Yoichi Mizukami and Kentaro Ushijima
Int. J. Mol. Sci. 2024, 25(23), 13145; https://doi.org/10.3390/ijms252313145 - 6 Dec 2024
Cited by 2 | Viewed by 1127
Abstract
Regenerative therapy involving stem cell transplantation has become an option for the radical treatment of diabetes mellitus. Disruption in the clock genes of stem cells affects the homeostasis of transplanted tissues. We examined the circadian rhythm of genes in transplanted adipose-derived mesenchymal stem [...] Read more.
Regenerative therapy involving stem cell transplantation has become an option for the radical treatment of diabetes mellitus. Disruption in the clock genes of stem cells affects the homeostasis of transplanted tissues. We examined the circadian rhythm of genes in transplanted adipose-derived mesenchymal stem cells derived from a patient with type 2 diabetes mellitus (T2DM-ADSC). The clock genes (PER2, CLOCK1, CRY1, and ARNTL[BMAL1]) exhibited similar daily fluctuations in phase and amplitude between a group transplanted with adipose-derived mesenchymal stem cells derived from a healthy individual (N-ADSC) and a group transplanted with T2DM-ADSC. The findings demonstrated that clock genes in stem cells are synchronized with those in living organisms. Next-generation sequencing was then employed to categorize genes that exhibited variation in expression between N-ADSC and T2DM-ADSC. MTATP8P1 and NDUFA7_2 gene expression was significantly reduced at two time points (ZT6 and ZT18), and daily fluctuations were lost. The present study reports, for the first time, that the circadian rhythms of MTATP8P1 and NDUFA7_2, genes involved in mitochondrial processes, are altered in T2DM-ADSC. Full article
(This article belongs to the Special Issue Using Model Organisms to Study Complex Human Diseases)
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17 pages, 5069 KiB  
Article
Investigating the Influence of a Tooth Absence on Facial Bone Growth Using a Porcine Model
by Dominika Szkopek, Piotr Wychowański, Kamil Zaworski, Blanka Seklecka, Rafał Starzyński, Paweł Lipiński, Kateryna Pierzynowska, Stefan G. Pierzynowski, Janine Donaldson, Łukasz Paczewski and Jarosław Woliński
Int. J. Mol. Sci. 2024, 25(23), 12509; https://doi.org/10.3390/ijms252312509 - 21 Nov 2024
Viewed by 941
Abstract
With the current state of knowledge regarding disorders of facial bone development, including anodontia, the development of a suitable animal model for preclinical studies is essential. The agenesis of dental buds occurs in about 25% of the human population. Prospects for treatment include [...] Read more.
With the current state of knowledge regarding disorders of facial bone development, including anodontia, the development of a suitable animal model for preclinical studies is essential. The agenesis of dental buds occurs in about 25% of the human population. Prospects for treatment include the use of growth factors, stem cells, and bioengineering. This study aimed to investigate the influence of a tooth absence on facial bone growth, develop a technique for the application of growth factors to the developing bone, and analyze the comparative effect of the application of selected active proteins on the growth of the maxilla and mandible. Piglets underwent germectomy, followed by computed tomography and X-ray; morphometric and histological analyses of the bones were performed, blood bone morphogenetic protein 2 and platelet-derived growth factor concentrations were determined, and the transcriptomic profile of the dentate ligament was analyzed using DNA microarrays. It was not possible to identify the most effective growth factor application algorithm for achieving normal jaw development. Normal mandibular bone structure and oral mucosa structure were observed in the germectomy groups with growth factor augmentation. The average height of the mandibular alveolar part in the area of the removed dental buds was significantly lower compared with that of the inoperable side, 3 months after surgery. However, no significant differences were found in the serum concentrations of BMP-2 and PDGF between groups. The animal model of bone development disorders (including anodontia) developed in the current study and the scheme for evaluating the efficacy and safety of the application of replacement therapy for craniofacial malformations are important in the development of the discipline and represent an important contribution to the introduction of treatment methods. Full article
(This article belongs to the Special Issue Using Model Organisms to Study Complex Human Diseases)
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