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Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0

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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: closed (31 December 2022) | Viewed by 25603

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Special Issue Editor

Dr. Timofey S. Rozhdestvensky

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Medical Faculty, Core Facility Transgenic Animal and Genetic Engineering Models (TRAM), University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany
Interests: genome editing; CRISPR-Cas9 technology; programmable DNA endonucleases; nervous system diseases; RNA biology; disease-associated RNAs; non-protein coding RNAs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Transgenic mouse models are essential for understanding the molecular mechanisms and pathogenicity of most human diseases. Research based on live mouse models is important to discover and/or improve methods for the prevention, diagnosis, and treatment of diseases.

This Special Issue aims to cover all areas of molecular-based research to study various human diseases using genetically engineered mouse models. It welcomes original research, review, and short communication articles on cellular and molecular analyses of transgenic mouse models in areas including, but not limited to, functional genomics of disease, epigenomics, proteomics, RNA biology, systems biology, approaches and methods of mouse genome editing, software tools, etc.

Topics of interest for the issue include:

Generation of transgenic mouse models and targeting constructs;
Mouse genome editing approaches;
Transgenic mouse models in cancer research;
Transgenic mouse models to study infectious diseases;
Transgenic mouse models for mitochondrial diseases.
Transgenic mouse models in:
Cardiovascular diseases;
Developmental disorders;
Digestive system diseases;
Endocrine system diseases;
Immune diseases;
Integumentary system diseases;
Lymphatic system diseases;
Metabolism, obesity, and metabolic diseases;
Nervous system diseases (including sensory organ disorders);
Reproductive system diseases;
Respiratory system diseases;
Skeletal and muscular system diseases;
Urinary system diseases.

Dr. Timofey S. Rozhdestvensky
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (12 papers)

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Research

Jump to: Review

13 pages, 2619 KiB

Open AccessArticle

by Olga A. Averina, Oleg A. Permyakov, Mariia A. Emelianova, Ekaterina A. Guseva, Olga O. Grigoryeva, Maxim L. Lovat, Anna E. Egorova, Andrei V. Grinchenko, Vadim V. Kumeiko, Maria V. Marey, Vasily N. Manskikh, Olga A. Dontsova, Mikhail Y. Vyssokikh and Petr V. Sergiev

Int. J. Mol. Sci. 2023, 24(10), 9106; https://doi.org/10.3390/ijms24109106 - 22 May 2023

Cited by 1 | Viewed by 1746

Abstract

A small protein, Mitoregulin (Mtln), localizes in mitochondria and contributes to oxidative phosphorylation and fatty acid metabolism. Mtln knockout mice develop obesity on a high-fat diet, demonstrating elevated cardiolipin damage and suboptimal creatine kinase oligomerization in muscle tissue. Kidneys heavily depend on the oxidative phosphorylation in mitochondria. Here we report kidney-related phenotypes in aged Mtln knockout mice. Similar to Mtln knockout mice muscle mitochondria, those of the kidney demonstrate a decreased respiratory complex I activity and excessive cardiolipin damage. Aged male mice carrying Mtln knockout demonstrated an increased frequency of renal proximal tubules’ degeneration. At the same time, a decreased glomerular filtration rate has been more frequently detected in aged female mice devoid of Mtln. An amount of Mtln partner protein, Cyb5r3, is drastically decreased in the kidneys of Mtln knockout mice. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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15 pages, 3066 KiB

Open AccessArticle

Limitations of Tamoxifen Application for In Vivo Genome Editing Using Cre/ER^T2 System

by Leonid A. Ilchuk, Nina I. Stavskaya, Ekaterina A. Varlamova, Alvina I. Khamidullina, Victor V. Tatarskiy, Vladislav A. Mogila, Ksenia B. Kolbutova, Sergey A. Bogdan, Alexey M. Sheremetov, Alexandr N. Baulin, Irina A. Filatova, Yulia Yu. Silaeva, Maxim A. Filatov and Alexandra V. Bruter

Int. J. Mol. Sci. 2022, 23(22), 14077; https://doi.org/10.3390/ijms232214077 - 15 Nov 2022

Cited by 5 | Viewed by 3339

Abstract

Inducible Cre-dependent systems are frequently used to produce both conditional knockouts and transgenic mice with regulated expression of the gene of interest. Induction can be achieved by doxycycline-dependent transcription of the wild type gene or OH-tamoxifen-dependent nuclear translocation of the chimeric Cre/ER^T2 protein. However, both of these activation strategies have some limitations. We analyzed the efficiency of knockout in different tissues and found out that it correlates with the concentration of the hydroxytamoxifen and endoxifen—the active metabolites of tamoxifen—measured by LC-MS in these tissues. We also describe two cases of Cdk8^{floxed/floxed}/Rosa-Cre-ER^T2 mice tamoxifen-induced knockout limitations. In the first case, the standard scheme of tamoxifen administration does not lead to complete knockout formation in the brain or in the uterus. Tamoxifen metabolite measurements in multiple tissues were performed and it has been shown that low recombinase activity in the brain is due to the low levels of tamoxifen active metabolites. Increase of tamoxifen dosage (1.5 fold) and duration of activation (from 5 to 7 days) allowed us to significantly improve the knockout rate in the brain, but not in the uterus. In the second case, knockout induction during embryonic development was impossible due to the negative effect of tamoxifen on gestation. Although DNA editing in the embryos was achieved in some cases, the treatment led to different complications of the pregnancy in wild-type female mice. We propose to use doxycycline-induced Cre systems in such models. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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20 pages, 6490 KiB

Open AccessArticle

Engineered Immature Testicular Tissue by Electrospun Mats for Prepubertal Fertility Preservation in a Bioluminescence Imaging Transgenic Mouse Model

by Chi-Huang Chen, Tsai-Chin Shih, Yung-Liang Liu, Yi-Jen Peng, Ya-Li Huang, Brian Shiian Chen and How Tseng

Int. J. Mol. Sci. 2022, 23(20), 12145; https://doi.org/10.3390/ijms232012145 - 12 Oct 2022

Viewed by 1565

Abstract

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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17 pages, 9561 KiB

Open AccessArticle

Examination of Longitudinal Alterations in Alzheimer’s Disease-Related Neurogenesis in an APP/PS1 Transgenic Mouse Model, and the Effects of P33, a Putative Neuroprotective Agent Thereon

by Titanilla Szögi, Emőke Borbély, Ildikó Schuster, Zsolt Bozsó, Miklós Sántha, Melinda E. Tóth, Botond Penke and Lívia Fülöp

Int. J. Mol. Sci. 2022, 23(18), 10364; https://doi.org/10.3390/ijms231810364 - 08 Sep 2022

Cited by 2 | Viewed by 1743

Abstract

Neurogenesis plays a crucial role in cognitive processes. During aging and in Alzheimer’s disease (AD), altered neurogenesis and neuroinflammation are evident both in C57BL/6J, APP_Swe/PS1_dE9 (Tg) mice and humans. AD pathology may slow down upon drug treatment, for example, in a previous study of our group P33, a putative neuroprotective agent was found to exert advantageous effects on the elevated levels of APP, Aβ, and neuroinflammation. In the present study, we aimed to examine longitudinal alterations in neurogenesis, neuroinflammation and AD pathology in a transgenic (Tg) mouse model, and assessed the putative beneficial effects of long-term P33 treatment on AD-specific neurological alterations. Hippocampal cell proliferation and differentiation were significantly reduced between 8 and 12 months of age. Regarding neuroinflammation, significantly elevated astrogliosis and microglial activation were observed in 6- to 7-month-old Tg animals. The amounts of the molecules involved in the amyloidogenic pathway were altered from 4 months of age in Tg animals. P33-treatment led to significantly increased neurogenesis in 9-month-old animals. Our data support the hypothesis that altered neurogenesis may be a consequence of AD pathology. Based on our findings in the transgenic animal model, early pharmacological treatment before the manifestation of AD symptoms might ameliorate neurological decline. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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Graphical abstract

15 pages, 2801 KiB

Open AccessArticle

Longterm Increased S100B Enhances Hippocampal Progenitor Cell Proliferation in a Transgenic Mouse Model

by Leticia Rodrigues, Krista Minéia Wartchow, Michael Buchfelder, Diogo Onofre Souza, Carlos-Alberto Gonçalves and Andrea Kleindienst

Int. J. Mol. Sci. 2022, 23(17), 9600; https://doi.org/10.3390/ijms23179600 - 24 Aug 2022

Cited by 2 | Viewed by 1433

Abstract

(1) The neurotrophic protein S100B is a marker of brain injury and has been associated with neuroregeneration. In S100Btg mice rendering 12 copies of the murine S100B gene we evaluated whether S100B may serve as a treatment option. (2) In juvenile, adult, and one-year-old S100Btg mice (female and male; n = 8 per group), progenitor cell proliferation was quantified in the subgranular zone (SGZ) and the granular cell layer (GCL) of the dentate gyrus with the proliferative marker Ki67 and BrdU (50 mg/kg). Concomitant signaling was quantified utilizing glial fibrillary acidic protein (GFAP), apolipoprotein E (ApoE), brain-derived neurotrophic factor (BDNF), and the receptor for advanced glycation end products (RAGE) immunohistochemistry. (3) Progenitor cell proliferation in the SGZ and migration to the GCL was enhanced. Hippocampal GFAP was reduced in one-year-old S100Btg mice. ApoE in the hippocampus and frontal cortex of male and BDNF in the frontal cortex of female S100Btg mice was reduced. RAGE was not affected. (4) Enhanced hippocampal neurogenesis in S100Btg mice was not accompanied by reactive astrogliosis. Sex- and brain region-specific variations of ApoE and BDNF require further elucidations. Our data reinforce the importance of this S100Btg model in evaluating the role of S100B in neuroregenerative medicine. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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14 pages, 9816 KiB

Open AccessArticle

Macrophage-Specific, Mafb-Deficient Mice Showed Delayed Skin Wound Healing

by Yuri Inoue, Ching-Wei Liao, Yuki Tsunakawa, I-Lin Tsai, Satoru Takahashi and Michito Hamada

Int. J. Mol. Sci. 2022, 23(16), 9346; https://doi.org/10.3390/ijms23169346 - 19 Aug 2022

Cited by 2 | Viewed by 2856

Abstract

Macrophages play essential roles throughout the wound repair process. Nevertheless, mechanisms regulating the process are poorly understood. MAFB is specifically expressed in the macrophages in hematopoietic tissue and is vital to homeostatic function. Comparison of the skin wound repair rates in macrophage-specific, MAFB-deficient mice (Mafb^f/f::LysM-Cre) and control mice (Mafb^f/f) showed that wound healing was significantly delayed in the former. For wounded GFP knock-in mice with GFP inserts in the Mafb locus, flow cytometry revealed that their GFP-positive cells expressed macrophage markers. Thus, macrophages express Mafb at wound sites. Immunohistochemical (IHC) staining, proteome analysis, and RT-qPCR of the wound tissue showed relative downregulation of Arg1, Ccl12, and Ccl2 in Mafb^f/f::LysM-Cre mice. The aforementioned genes were also downregulated in the bone marrow-derived, M2-type macrophages of Mafb^f/f::LysM-Cre mice. Published single-cell RNA-Seq analyses showed that Arg1, Ccl2, Ccl12, and Il-10 were expressed in distinct populations of MAFB-expressing cells. Hence, the MAFB-expressing macrophage population is heterogeneous. MAFB plays the vital role of regulating multiple genes implicated in wound healing, which suggests that MAFB is a potential therapeutic target in wound healing. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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19 pages, 2419 KiB

Open AccessArticle

Reference Genes across Nine Brain Areas of Wild Type and Prader-Willi Syndrome Mice: Assessing Differences in Igfbp7, Pcsk1, Nhlh2 and Nlgn3 Expression

by Delf-Magnus Kummerfeld, Boris V. Skryabin, Juergen Brosius, Sergey Y. Vakhrushev and Timofey S. Rozhdestvensky

Int. J. Mol. Sci. 2022, 23(15), 8729; https://doi.org/10.3390/ijms23158729 - 05 Aug 2022

Cited by 2 | Viewed by 2784

Abstract

Prader–Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by the deletion or inactivation of paternally expressed imprinted genes at the chromosomal region 15q11–q13. The PWS-critical region (PWScr) harbors tandemly repeated non-protein coding IPW-A exons hosting the intronic SNORD116 snoRNA gene array that is predominantly expressed in brain. Paternal deletion of PWScr is associated with key PWS symptoms in humans and growth retardation in mice (PWScr model). Dysregulation of the hypothalamic–pituitary axis (HPA) is thought to be causally involved in the PWS phenotype. Here we performed a comprehensive reverse transcription quantitative PCR (RT-qPCR) analysis across nine different brain regions of wild-type (WT) and PWScr mice to identify stably expressed reference genes. Four methods (Delta Ct, BestKeeper, Normfinder and Genorm) were applied to rank 11 selected reference gene candidates according to their expression stability. The resulting panel consists of the top three most stably expressed genes suitable for gene-expression profiling and comparative transcriptome analysis of WT and/or PWScr mouse brain regions. Using these reference genes, we revealed significant differences in the expression patterns of Igfbp7, Nlgn3 and three HPA associated genes: Pcsk1, Pcsk2 and Nhlh2 across investigated brain regions of wild-type and PWScr mice. Our results raise a reasonable doubt on the involvement of the Snord116 in posttranscriptional regulation of Nlgn3 and Nhlh2 genes. We provide a valuable tool for expression analysis of specific genes across different areas of the mouse brain and for comparative investigation of PWScr mouse models to discover and verify different regulatory pathways affecting this complex disorder. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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16 pages, 10881 KiB

Open AccessArticle

Tracking Immature Testicular Tissue after Vitrification In Vitro and In Vivo for Pre-Pubertal Fertility Preservation: A Translational Transgenic Mouse Model

by Buo-Jia Lu, Ya-Li Huang, Yung-Liang Liu, Brian Shiian Chen, Bou-Zenn Lin and Chi-Huang Chen

Int. J. Mol. Sci. 2022, 23(15), 8425; https://doi.org/10.3390/ijms23158425 - 29 Jul 2022

Cited by 2 | Viewed by 1640

Abstract

Pediatric cancer survivors experiencing gonadotoxic chemoradiation therapy may encounter subfertility or permanent infertility. However, previous studies of cryopreservation of immature testicular tissue (ITT) have mainly been limited to in vitro studies. In this study, we aim to evaluate in vitro and in vivo bioluminescence imaging (BLI) for solid surface-vitrified (SSV) ITT grafts until adulthood. The donors and recipients were transgenic and wild-type mice, respectively, with fresh ITT grafts used as the control group. In our study, the frozen ITT grafts remained intact as shown in the BLI, scanning electron microscopy (SEM) and immunohistochemistry (IHC) analyses. Graft survival was analyzed by BLI on days 1, 2, 5, 7, and 31 after transplantation. The signals decreased by quantum yield between days 2 and 5 in both groups, but gradually increased afterwards until day 31, which were significantly stronger than day 1 after transplantation (p = 0.008). The differences between the two groups were constantly insignificant, suggesting that both fresh and SSV ITT can survive, accompanied by spermatogenesis, until adulthood. The ITT in both groups presented similar BLI intensity and intact cells and ultrastructures for spermatogenesis. This translational model demonstrates the great potential of SSV for ITT in pre-pubertal male fertility preservation. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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12 pages, 5468 KiB

Open AccessArticle

Therapeutic Effects of Quetiapine and 5-HT_1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice

by Yukiko Ochiai, Masayo Fujita, Yoko Hagino, Kazuto Kobayashi, Ryoichi Okiyama, Kazushi Takahashi and Kazutaka Ikeda

Int. J. Mol. Sci. 2022, 23(13), 7436; https://doi.org/10.3390/ijms23137436 - 04 Jul 2022

Cited by 5 | Viewed by 1981

Abstract

Some diseases that are associated with dopamine deficiency are accompanied by psychiatric symptoms, including Parkinson’s disease. However, the mechanism by which this occurs has not been clarified. Previous studies found that dopamine-deficient (DD) mice exhibited hyperactivity in a novel environment. This hyperactivity is improved by clozapine and donepezil, which are used to treat psychiatric symptoms associated with dopamine deficiency (PSDD). We considered that DD mice could be used to study PSDD. In the present study, we sought to identify the pharmacological mechanism of PSDD. We conducted locomotor activity tests by administering quetiapine and drugs that have specific actions on serotonin (5-hydroxytryptamine [5-HT]) receptors and muscarinic receptors. Changes in neuronal activity that were induced by drug administration in DD mice were evaluated by examining Fos immunoreactivity. Quetiapine suppressed hyperactivity in DD mice while the 5-HT_1A receptor antagonist WAY100635 inhibited this effect. The number of Fos-positive neurons in the median raphe nucleus increased in DD mice that exhibited hyperactivity and was decreased by treatment with quetiapine and 5-HT_1A receptor agonists. In conclusion, hyperactivity in DD mice was ameliorated by quetiapine, likely through 5-HT_1A receptor activation. These findings suggest that 5-HT_1A receptors may play a role in PSDD, and 5-HT_1A receptor-targeting drugs may help improve PSDD. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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Review

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14 pages, 1884 KiB

Open AccessReview

Vertebrate Animal Models of RP59: Current Status and Future Prospects

by Steven J. Fliesler, Sriganesh Ramachandra Rao, Mai N. Nguyen, Mahmoud Tawfik KhalafAllah and Steven J. Pittler

Int. J. Mol. Sci. 2022, 23(21), 13324; https://doi.org/10.3390/ijms232113324 - 01 Nov 2022

Viewed by 1451

Abstract

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for the synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing “knowledge gaps” in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset or to dampen the severity or progression of RP59. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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26 pages, 4508 KiB

Open AccessReview

E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging

by Morgan Ramón-Landreau, Cristina Sánchez-Puelles, Noelia López-Sánchez, Anna Lozano-Ureña, Aina M. Llabrés-Mas and José M. Frade

Int. J. Mol. Sci. 2022, 23(20), 12093; https://doi.org/10.3390/ijms232012093 - 11 Oct 2022

Cited by 1 | Viewed by 2351

Abstract

E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis, as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex, as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-β (Aβ) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both the cerebral cortex and hippocampus at 3-6 months of age. Here, we analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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15 pages, 987 KiB

Open AccessReview

Transgenic Mice for the Translational Study of Neuropathic Pain and Dystonia

by Damiana Scuteri, Kengo Hamamura, Chizuko Watanabe, Paolo Tonin, Giacinto Bagetta and Maria Tiziana Corasaniti

Int. J. Mol. Sci. 2022, 23(15), 8580; https://doi.org/10.3390/ijms23158580 - 02 Aug 2022

Cited by 1 | Viewed by 1821

Abstract

Murine models are fundamental in the study of clinical conditions and the development of new drugs and treatments. Transgenic technology has started to offer advantages in oncology, encompassing all research fields related to the study of painful syndromes. Knockout mice or mice overexpressing genes encoding for proteins linked to pain development and maintenance can be produced and pain models can be applied to transgenic mice to model the most disabling neurological conditions. Due to the association of movement disorders with sensitivity and pain processing, our group focused for the first time on the role of the torsinA gene GAG deletion—responsible for DYT1 dystonia—in baseline sensitivity and neuropathic responses. The aim of the present report are to review the complex network that exists between the chaperonine-like protein torsinA and the baseline sensitivity pattern—which are fundamental in neuropathic pain—and to point at its possible role in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 3.0)

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