Mouse Strains

J:NU Mouse Strain

By October 15, 2019 No Comments

Overview

J:NU, also known as outbred athymic nude, is an outbred strain of nude mouse that is severely immunodeficiency and used in immunology research.[1]

History

Like the related inbred strain NU/J, J:NU mice are descended from the original batch of nude mice identified by Dr Norman Grist in the early 1960s. Grist was working at Ruchill hospital in Glasgow and observed that some of his mice had spontaneously acquired a mutation that led to loss of thymus, immune deficiency and hairlessness.

The Jackson Laboratory imported a stock of outbred nude mice in 1975. J:NU was developed from cryopreserved NIH stocks which were then crossed with athymic nudes via in vitro fertilization to ensure high genetic variability. Since then, the mice have been maintained by scrupulous outbreeding and avoidance of sibling pairs.[1][2]

Physical Characteristics

J:NU mice are described as “nude” because they have no fur, and so appear pink and wrinkled. They are athymic i.e. they do not possess a thymus. They are also smaller than normal non-nude mice and their whiskers are either absent or “crinkled”.[1][2]

Behavioral Characteristics & Handling

Since these mice are severely immune deficient, it is necessary at all times to keep and handle them under as sterile conditions as possible. Researchers should only handle these mice when absolutely necessary, to minimize the risk of unwanted infection. The use of gloves and face masks is recommended.

Studies looking at J:NU mouse behavior in mazes and other apparatuses could not be found. Since J:NU are highly genetically heterogeneous, it is possible that their behavioral predispositions will also vary widely and be unpredictable.

Health Characteristics

These mice are homozygous for the mutant allele nu of the gene Foxn1. Foxn1 encodes a protein called forkhead box protein 1, a transcription factor expressed in the thymus and associated with keratin production. The nu mutation is a point mutation that introduces a stop codon and truncates the transcription factor before its DNA binding domain, rendering it non-functional.[1]

Without sufficient levels of forkhead box protein 1, J:NU is left severely immunodeficient. T cell precursors are unable to develop into mature T cells, meaning functional T cells are absent from J:NU’s blood plasma, and the mice are susceptible to viral infection. B cells, macrophages, natural killer cells, APCs and the complement system are present.[3]

Major Experimental Uses

J:NU mice, like NU/J, are primarily of interest for immunological research, especially research into athymism, T cell deficiency and general immune deficiency. Their immune system is still too functional however to make them a good model for severe combined immunodeficiency (SCID).

Their lack of a proper immune response means they are also very receptive to xenotransplantation, and so can be used by oncologists as hosts for tumor cells to allow the testing of anti-cancer drugs. They are not suitable however for the study of leukemia or lymphoma, since these cancers will be resisted by their robust NK cell response.[1]

Compared to NU/J and B6-nude, J:NU mice are much more genetically heterogeneous and so their tumor growth will be variable. Nonetheless, their genetic diversity makes them stronger than inbred alternatives which may aid in the testing of more severe cancers.[4]

References

  1. 007850 – J:NU. 2019. 007850 – J:NU. [ONLINE] Available at: https://www.jax.org/strain/007850. [Accessed 23 September 2019].
  2. 002019 – NU/J. 2019. 002019 – NU/J. [ONLINE] Available at: https://www.jax.org/strain/002019. [Accessed 23 September 2019].
  3. Saulius Žuklys, Adam Handel, Saule Zhanybekova, Fatima Govani, Marcel Keller, Stefano Maio, Carlos E Mayer, Hong Ying Teh, Katrin Hafen, Giuseppe Gallone, Thomas Barthlott, Chris P Ponting & Georg A Hollände. 2016. Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells. Nature Immunology. 17. 1206-1215.
  4. The Jackson Laboratory. 2019. Immunodeficient Mice for Cancer Studies: Which host strain should I use?. [ONLINE] Available at: https://www.jax.org/news-and-insights/jax-blog/2013/july/which-host-strain-should-i-use. [Accessed 23 September 2019].

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