(Newswire.net — May 20, 2022) — In laboratory mice, one or more genes are turned off; such mice are known as knockout mice or genetically modified mice. For gene knocking, scientists either disrupt a gene sequence or replace a gene sequence with another gene sequence; modern genetic engineering techniques are used to create knockout mice.
The specific functions of a knocked gene can be determined by comparing the physiological and behavioral activities of a knockout mouse with a normal mouse. Knockout mice are used to provide information about the normal functioning of the knocked-out gene and elaborate on the behavioral, developmental, and biochemical activities linked with the knocked-out gene.
Strains of Knockout mice
Knockout mice have thousands of various strains, and they are named after the name of gene knocked out in them. For instance, a mouse in which the p53 gene is knocked out is called knockout mouse p53. The p53 knocking helps to treat cancer because it controls cell division. Few of the mice models are named after their behaviors or physical characteristics.
The Procedure for Creating Knockout Mice
The knockout mice are created by replacing the gene to be knocked out with an identical sequenced novel gene. It can be done at the embryonic stem cell level with the help of electroporation or in gonads (sperm and ovum).
Figure: Illustrating the layout of creating knockout mice
What are Knockout Mice Used for?
The mouse has similarities with the human genome; therefore, knockout mice have an inclusive role in various human genome-based studies, including:
Figure: Genome similarities of humans and mice
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Pathological Studies
Knockout mice are used to evaluate the involvement of genes in various functions and the association of these genes in the pathogenesis of numerous diseases. Several genetic anomalies, gene-linked diseases, and pathological changes concerning the genome can be studied through knockout mice.
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Behavioral Research
Knockout mice are a useful gizmo for exploring the mechanisms behind an individual’s behavior and opening new windows in the field of neuroendocrinology. The use of knockout mice in endocrinology has various important facts: without drug impacts the gene product can be eliminated, various endogenous factors are easily determined through genetic manipulations, and a gene of the specific role is knocked out precisely. The controlled timing and placement of the target have boosted the endocrinological studies.
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Nutritional and Metabolic Research
Nutrition is direct with the health as nutritional deficiency has adverse effects on growth, immunity, and reproduction, but excess of this nutrient may also lead to diseases Viz. High fat (lipids) contents increase cholesterol and heart disorders, and a high vitamin D concentration increases the renal calculi.
However, there is variation in individual response to the dietary nutrients that depends on an individual’s genetic makeup. Genes are responsible for metabolic responses, nutrient absorption, and body reaction against these nutrients. The advanced molecular techniques enable scientists to explore gene and dietary nutrient interaction.
Earlier it was focused on evaluating the role of gene expression in nutrient regulation. Transgenic techniques were used to explore the role of gene expression and nutrient metabolism. Recently studies are going on gene knocking by targeting the specific gene, and it is successful by using knockout mice. The tissue-specific knockout mice are mainly used in nutritional and metabolic research. The knockout mice help explore the functioning of a specific gene in metabolism and the impact of specific gene mutations on metabolism.
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Thermoregulation Studies
The use of gene knockout models in thermoregulation studies has been increased to evaluate various genotypic and phenotypic responses. During thermoregulation, various endogenous mediators play a pivotal role, and the influence of these mediators has been explored with the help of these models.
Various responses have been observed due to mutant strains and wild-type strains that endorse the role of genomics and the use of genetic models for physiological studies. A little discrepancy in corollary is reported concerning the use of these gene knockout models. But for in vivo genomic studies, knockout mice play an inclusive role.
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Pharmacological Studies
The role of various drugs (cytokines, chemokines, hormones, and chemical substances) as a therapeutic agent and their effect on physiological conditions can be explored by using mice models. In various conditions, specifically knockout mice models are needed, for instance, in the case of the brain’s adenosine receptors as a therapeutic target.
The knockout mice have knocked out the genes for either A1R or A2AR, and both were used. Adenosine has receptors A1R and A2AR as potential regulators of neurodegeneration and psychiatric conditions, respectively. Adenosine binds with A1R receptors, blocks the release of glutamate (release from brain neurons), and inhibits excitability. Similarly, A2A-receptors of adenosine are involved in blocking the release of dopamine.
The mechanism of action of various drugs or potential therapeutic agents can be explored with the help of knockout mice. In the discovery of new potential therapeutic agents, knockout mice play a substantial role.
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Immunological Studies
Due to precise single genes being knocked out, physiological and immunological research have been revolutionized with knockout mice. The phenotypic responses of immune cells are noticed by knocking out a specific gene. The T-Lymphocytes production, maturation, positive and negative impacts, activation pathways, signaling pathways, co-stimulation, and regulatory mechanisms have been explored with the help of knockout mice.
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Oncological Research
Knockout mice are useful in exploring the genes associated with various cancerous conditions, and further, they also help treat those cancers. For instance, with the help of knockout mice, a tumor suppressor gene termed the p53 gene was explored, whose mutation occurs during breast cancer in humans. It was accomplished by a comparative study of phenotypic characteristics of mice with p53 knockout and normal mice.
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