Insights on FoxN1 Biological Significance and Usages of the "nude" Mouse in Studies of T-lymphopoiesis

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2012 Oct 24

PMID 23091413

Citations 26

Authors

Zhijie Zhang

Preston Burnley

Brandon Coder

Dong-Ming Su

Affiliations

Soon will be listed here.

Abstract

Mutation in the "nude" gene, i.e. the FoxN1 gene, induces a hairless phenotype and a rudimentary thymus gland in mice (nude mouse) and humans (T-cell related primary immunodeficiency). Conventional FoxN1 gene knockout and transgenic mouse models have been generated for studies of FoxN1 gene function related to skin and immune diseases, and for cancer models. It appeared that FoxN1's role was fully understood and the nude mouse model was fully utilized. However, in recent years, with the development of inducible gene knockout/knockin mouse models with the loxP-Cre(ER(T)) and diphtheria toxin receptor-induced cell abolished systems, it appears that the complete repertoire of FoxN1's roles and deep-going usage of nude mouse model in immune function studies have just begun. Here we summarize the research progress made by several recent works studying the role of FoxN1 in the thymus and utilizing nude and "second (conditional) nude" mouse models for studies of T-cell development and function. We also raise questions and propose further consideration of FoxN1 functions and utilizing this mouse model for immune function studies.

Citing Articles

Recombinant FOXN1 fusion protein increases T cell generation in old mice.

Zhao J, Hu R, Lai K, Zhang Z, Lai L Front Immunol. 2024; 15:1423488.

PMID: 39072332 PMC: 11272594. DOI: 10.3389/fimmu.2024.1423488.

A missense mutation in Lama3 causes androgen alopecia.

Ji Z, Ren W, He S, Wu H, Yuan B, Chen J Sci Rep. 2023; 13(1):20818.

PMID: 38012251 PMC: 10682005. DOI: 10.1038/s41598-023-48337-5.

A nude mutant rat derived from Sprague Dawley-National Institute of Nutrition rat colony with normal thymus: A potential model for noncommunicable diseases.

Motha S, Patil P, Ramavat R, Myadara S, H Qadri S Indian J Pharmacol. 2023; 55(5):299-306.

PMID: 37929408 PMC: 10751523. DOI: 10.4103/ijp.ijp_173_23.

Administration of recombinant FOXN1 protein attenuates Alzheimer's pathology in mice.

Zhao J, Zhang Z, Lai K, Lai L Brain Behav Immun. 2023; 113:341-352.

PMID: 37541395 PMC: 10528256. DOI: 10.1016/j.bbi.2023.07.027.

MicroRNAs as the Critical Regulators of Forkhead Box Protein Family in Pancreatic, Thyroid, and Liver Cancers.

Akhlaghipour I, Fanoodi A, Zangouei A, Taghehchian N, Khalili-Tanha G, Moghbeli M Biochem Genet. 2023; 61(5):1645-1674.

PMID: 36781813 DOI: 10.1007/s10528-023-10346-4.

References

Frank J, Pignata C, Panteleyev A, Prowse D, Baden H, Weiner L . Exposing the human nude phenotype. Nature. 1999; 398(6727):473-4. DOI: 10.1038/18997. View

Mohtashami M, Zuniga-Pflucker J . Three-dimensional architecture of the thymus is required to maintain delta-like expression necessary for inducing T cell development. J Immunol. 2006; 176(2):730-4. DOI: 10.4049/jimmunol.176.2.730. View

Pignata C, Fusco A, Amorosi S . Human clinical phenotype associated with FOXN1 mutations. Adv Exp Med Biol. 2010; 665:195-206. View

Nehls M, Kyewski B, Messerle M, Waldschutz R, Schuddekopf K, Smith A . Two genetically separable steps in the differentiation of thymic epithelium. Science. 1996; 272(5263):886-9. DOI: 10.1126/science.272.5263.886. View

Metzger D, Chambon P . Site- and time-specific gene targeting in the mouse. Methods. 2001; 24(1):71-80. DOI: 10.1006/meth.2001.1159. View

Corbeaux T, Hess I, Swann J, Kanzler B, Haas-Assenbaum A, Boehm T . Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc Natl Acad Sci U S A. 2010; 107(38):16613-8. PMC: 2944754. DOI: 10.1073/pnas.1004623107. View

Manley N, Capecchi M . The role of Hoxa-3 in mouse thymus and thyroid development. Development. 1995; 121(7):1989-2003. DOI: 10.1242/dev.121.7.1989. View

Bleul C, Corbeaux T, Reuter A, Fisch P, Monting J, Boehm T . Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature. 2006; 441(7096):992-6. DOI: 10.1038/nature04850. View

Weiner L, Han R, Scicchitano B, Li J, Hasegawa K, Grossi M . Dedicated epithelial recipient cells determine pigmentation patterns. Cell. 2007; 130(5):932-42. DOI: 10.1016/j.cell.2007.07.024. View

10.

Schlake T, Schorpp M, Nehls M, Boehm T . The nude gene encodes a sequence-specific DNA binding protein with homologs in organisms that lack an anticipatory immune system. Proc Natl Acad Sci U S A. 1997; 94(8):3842-7. PMC: 20529. DOI: 10.1073/pnas.94.8.3842. View

11.

Lee D, Prowse D, Brissette J . Association between mouse nude gene expression and the initiation of epithelial terminal differentiation. Dev Biol. 1999; 208(2):362-74. DOI: 10.1006/dbio.1999.9221. View

12.

Feil R, Wagner J, Metzger D, Chambon P . Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun. 1997; 237(3):752-7. DOI: 10.1006/bbrc.1997.7124. View

13.

Bleul C, Boehm T . Chemokines define distinct microenvironments in the developing thymus. Eur J Immunol. 2000; 30(12):3371-9. DOI: 10.1002/1521-4141(2000012)30:12<3371::AID-IMMU3371>3.0.CO;2-L. View

14.

Shultz L . Immunological mutants of the mouse. Am J Anat. 1991; 191(3):303-11. DOI: 10.1002/aja.1001910310. View

15.

Schuddekopf K, Schorpp M, Boehm T . The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain. Proc Natl Acad Sci U S A. 1996; 93(18):9661-4. PMC: 38485. DOI: 10.1073/pnas.93.18.9661. View

16.

Zook E, Krishack P, Zhang S, Zeleznik-Le N, Firulli A, Witte P . Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood. 2011; 118(22):5723-31. PMC: 3228493. DOI: 10.1182/blood-2011-03-342097. View

17.

Scheiff J, Cordier A, Haumont S . The thymus of Nu/+ mice. Anat Embryol (Berl). 1978; 153(2):115-22. DOI: 10.1007/BF00343368. View

18.

Markert M, Marques J, Neven B, Devlin B, McCarthy E, Chinn I . First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2010; 117(2):688-96. PMC: 3031487. DOI: 10.1182/blood-2010-06-292490. View

19.

Cheng L, Guo J, Sun L, Fu J, Barnes P, Metzger D . Postnatal tissue-specific disruption of transcription factor FoxN1 triggers acute thymic atrophy. J Biol Chem. 2009; 285(8):5836-47. PMC: 2820809. DOI: 10.1074/jbc.M109.072124. View

20.

Lindsay E, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T . Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature. 2001; 410(6824):97-101. DOI: 10.1038/35065105. View