A nude mouse is a
laboratory mouse
The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species '' Mus musculus''. They are the most commonly ...
from a strain with a
genetic mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
that causes a deteriorated or absent
thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or '' T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders ...
, resulting in an inhibited
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
due to a greatly reduced number of
T cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
. The phenotype (main outward appearance) of the mouse is a lack of body hair, which gives it the "nude" nickname. The nude mouse is valuable to research because it can receive many different types of tissue and tumor grafts, as it mounts no
rejection response. These
xenografts
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenograf ...
are commonly used in research to test new methods of imaging and treating tumors. The genetic basis of the nude mouse mutation is a disruption of the
FOXN1
Forkhead box protein N1 is a protein that in humans is encoded by the ''FOXN1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...
gene.
Nomenclature
The nomenclature for the nude mouse has changed several times since their discovery. Originally they were described as ''nu'' and this was updated to ''Hfh11nu'' when the mutated gene was identified as a mutation in the HNF-3/forkhead homolog 11 gene. Then in 2000 the
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
responsible for the mutation was identified as a member of the Fox gene family and the nomenclature was updated to ''Foxn1nu''.
History and significance
Nude mice were first discovered in 1962 by Dr. Norman R. Grist at
Ruchill
Ruchill () is a district in the city of Glasgow, Scotland. It lies within the Canal Ward of north Glasgow in the Ruchill Community Council area between the Maryhill and Possilpark areas of the city. It has traditionally been characterised by ...
Hospital's Brownlee virology laboratory in
Glasgow
Glasgow ( ; sco, Glesca or ; gd, Glaschu ) is the most populous city in Scotland and the fourth-most populous city in the United Kingdom, as well as being the 27th largest city by population in Europe. In 2020, it had an estimated popu ...
. Because they lack a thymus, nude mice cannot generate mature
T lymphocytes
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...
. Therefore they are unable to mount many types of adaptive
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which coul ...
s, including:
#antibody formation that requires
CD4
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ce ...
+
helper T cells
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
#
cell-mediated immune responses, which require CD4+ and/or CD8+ T cells
#delayed-type
hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...
responses (require CD4+ T cells)
#killing of virus-infected or
malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
cells (requires
CD8+
cytotoxic T cells
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
)
#
graft rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient a ...
(requires both CD4+ and CD8+ T cells)
Because of the above features, nude mice have served in the laboratory to gain insights into the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
,
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
, solid
tumors,
AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
and other forms of
immune deficiency
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
as well as
leprosy
Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...
.
Moreover, the absence of functioning T cells prevents nude mice from rejecting not only
allografts
Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or ...
, but they cannot even reject
xenografts
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenograf ...
; that is, grafts of tissue from another species.
Most strains of nude mice are slightly "leaky" and do have a few T cells, especially as they age. For this reason, nude mice are less popular in research today, since
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
with more complete defects in the immune system have been constructed (e.g.
RAG1
Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the ''RAG1'' gene.
The RAG1 and RAG2 genes are largely conserved in humans. 55.99% and 55.98% of the encoded amino acids contain no reported variants, r ...
and
RAG2
Recombination activating gene 2 protein (also known as RAG-2) is a lymphocyte-specific protein encoded by RAG2 gene on human chromosome 11. Together with RAG1 protein, RAG2 forms a V(D)J recombinase, a protein complex required for the process of V( ...
knockout mice).
Genetics
Nude mice have a spontaneous deletion in the FOXN1 gene. (Humans with mutations in FOXN1 also are athymic and immune deficient.
) Mice with a targeted deletion in the FOXN1 ("knockout" mice) also show the "nude" phenotype. Since ''nude'' females have underdeveloped mammary glands and are unable to effectively nurse their young, nude males are bred with
heterozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
...
females.
Life span
The life span of nude mice is normally 6 months to a year. In controlled, germ free environments and with antibiotic treatments found in many laboratories that routinely use nude mice, they can live almost as long as normal mice (18 months to two years).
See also
*
Skinny pig
*
Earmouse
References
*''The Nude Mouse in Experimental and Clinical Research (Vol.1).'' Fogh, J; Giovanella, B.C.(eds) Academic Press, 1978,
*''The Nude Mouse in Experimental and Clinical Research (Vol.2).'' Fogh, J; Giovanella, B.C.(eds) Academic Press, 1982,
External links
A nude mouse can accept tissue grafts from a variety of species
{{DEFAULTSORT:Nude Mouse
Immunology mice