. Author manuscript; available in PMC: 2023 Jan 1.

Published in final edited form as: Immunol Rev. 2021 Nov 8;305(1):43–58. doi: 10.1111/imr.13034

Table 1.

Transcriptional and epigenetic regulators associated with thymic development and maintenance.

Factor	Mouse model	Phenotype
Aire	Constitutive loss-of-function mutation	Aire deficiency provoked multiorgan autoimmunity.³⁰
Aff4	Constitutive KO	Ablation of Aff4 induced a nude-like phenotype. Embryos exhibited thymic hyplopasia became that was more severe when one Foxn1 allele was defective.¹⁹⁷
Eed	Cre-Foxn1 Eed^fl/fl Cre-β5t Eed^fl/fl	Deficiency of Eed resulted in thymic atrophy decrementing TCR diversity.^189,191
Eya1	Constitutive KO	Eya1 deficiency compromised the formation of thymus and parathyroid structures.^54,55
Gata3	Constitutive KO	Ablation of Gata3 impeded developmental progression of the thymus/parathyroid primordia.^57,58
HDACs	Cre-Foxn1 HDAC3^fl/fl	Deficiency of HDAC3 in thymus inhibited mTEC development and TRA expression, and lead to autoimmunity.¹⁸³
Hoxa3	Constitutive KO	Ablation of Hoxa3 altered the formation of the thymus, thyroid and parathyroid organs. Hoxa3 deficiency reduced Pax1 and Pax9 expression levels.^52,53
Fezf2	Constitutive KO and Cre-Foxn1 Fezf2^fl/−	Fezf2 regulates Aire-independent TRA expression. Knocking out Fezf2 caused autoimmunity in several peripheral tissues. ³¹
Foxn1	Nude mice	Deficiency of Foxn1 disrupted thymic development and hair growth. Foxn1 was also required for postnatal TEC maintenance.^39-41
Foxa1/2	Cre-Foxn1 Foxa1^fl/fl Foxa2^fl/fl	Ablation of both Foxa1 and Foxa2 reduced thymi size, and increased the ratio of mTEC:cTEC.¹⁷⁸
Meis1	CreERT2-K14 Meis1^fl/fl	Meis1 ablation in adult mice leaded to loss of thymus size. T cell development was also compromised.¹⁷³
Myc	Cre-Foxn1 Myc^fl/fl and Cre-Foxn1 MycTg	Myc deficiency reduced the proliferation of TEC but the differentiation to mTEC was unaltered. Ectopic Myc expression increased TEC proliferation and thymus size.^166,167
NF-kB	Constitutive KO of Tnfrsf11a, Traf6, Cd40, or Relb. Constitutive expression of mutated Nik (G855R)	Inhibition of NF-kB signaling resulted in thymic medullary atrophy, leading to autoimmunity.^{63,73,75,81,198,199}
p53	Cre-Foxn1 p53^fl/fl	Ablation of p53 inhibited mTEC differentiation, thymocyte maturation and compromised peripheral tolerance in 6-7 month old mice.¹⁶⁰
p63	Constitutive KO	Deficiency in p63 resulted in thymic hyploplasia during embryonic development.^91,92
Pou2f3	Constitutive KO	Pou2f3 deficiency resulted in loss of thymic tuft cells.^32,33
RBPJ	Cre-Foxn1 Rbpj^fl/fl, CreER-Foxa2 Notch^fl/fl, Cre-Foxn1 Rosa^N1-IC, RBPJ ^fl/fl Cre-Foxn1; Rosa ^rtTA; Tet^on-RBPJ-HA	Deficiency of either Notch1 or RBPJ inhibited the establishment of mTEC progenitor cells during fetal development, and reduced the mTEC compartment postnatally.^179,180
Six1	Constitutive KO	Six1^−/− embryos failed to generate the thymus/parathyroid common primordia. Foxn1 expression was reduced in the common primordia in Six1^−/− embryos.⁵⁵
Tbx1	Cre-Foxn1 R26-iTbx	Ectopic expression of Tbx1 reduced proliferation and blocked differentiation of TEC progenitors at embryonic stage. Overexpression of Tbx1 inhibited Foxn1 expression but induced targets genes of the Polycomb Repressive Complex (PRC) 2.^188,189
Pax1	Constitutive KO	Pax1 ablation produced a hypoplastic thymus with deficient thymocyte development.^49,200
Pax9	Constitutive KO	Organs derived from the third pharyngeal pouch, including the thymus, were compromised.⁵⁰