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Genetically modified mice as a tool for the study of human diseases

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Abstract

Modeling a human disease is an essential part of biomedical research. The recent advances in the field of molecular genetics made it possible to obtain genetically modified animals for the study of various diseases. Not only monogenic disorders but also chromosomal and multifactorial disorders can be mimicked in lab animals due to genetic modification. Even human infectious diseases can be studied in genetically modified animals. An animal model of a disease enables the tracking of its pathogenesis and, more importantly, to test new therapies. In the first part of this paper, we review the most common DNA modification technologies and provide key ideas on specific technology choices according to the task at hand. In the second part, we focus on the application of genetically modified mice in studying human diseases.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

AAV:

Adeno-associated virus

BMMC:

Bone marrow mononuclear cell

Cu/Zn-SOD:

Cu/Zn superoxide dismutase-1

DMD:

Duchenne muscular dystrophy

DSB:

Double-strand breaks

ESC:

Embryonic stem cells

FUS:

Fused in sarcoma

GM:

Gene modified

GWAS:

Genome-wide association studies

HBV:

Hepatitis B virus

HDL:

High-density lipoprotein

LDLR:

Low-density lipoprotein receptor

HDR:

Homology directed repair

HLA:

Human leukocyte antigens

HPRT:

Hypoxanthine phosphoribosyl transferase

HPV:

Human papillomaviruses

LNS:

Lesch–Nyhan syndrome

KI:

Knock-in

KO:

Knock-out

NHEJ:

Non-homologous end joining

NOD:

Non-obese diabetes

sgRNA:

Single guide RNA

siRNA:

Small interfering RNA

SNP:

Single nucleotide polymorphism

ORFs:

Open reading frames

PV:

Poliovirus

PVR:

Poliovirus receptor

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

SMA:

Spinal muscular atrophy

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Funding

The work was supported by the Russian Science Foundation project no. 22-15-00227 and by grant 075-15-2021-668 (29.07.2021) from the UNU Transgenbank. Chapter “Concerns” section was financed through the Russian Science Foundation and all other parts were performed by the grant support of the UNU Transgenbank.

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Authors and Affiliations

  1. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia, 119334

    Alexandra V. Bruter, Ekaterina A. Varlamova, Yulia D. Okulova, Victor V. Tatarskiy & Maxim A. Filatov

  2. Federal State Budgetary Institution “National Medical Research Center of Oncology Named After N.N. Blokhin” of the Ministry of Health of the Russian Federation, Research Institute of Carcinogenesis, Moscow, Russia, 115478

    Alexandra V. Bruter & Ekaterina A. Varlamova

  3. Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia, 119334

    Yulia Y. Silaeva

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  1. Alexandra V. Bruter
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All authors contributed to the review conception. The first draft of the manuscript was written by AVB, images were prepared by EAV and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Maxim A. Filatov.

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Bruter, A.V., Varlamova, E.A., Okulova, Y.D. et al. Genetically modified mice as a tool for the study of human diseases. Mol Biol Rep 51, 135 (2024). https://doi.org/10.1007/s11033-023-09066-0

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