TABLE 1.

Summary of metabolic studies with Irx3 or Irx5 mutant mice.

Mouse model	Transgenic system	Target tissue		Metabolic phenotype		References
Irx3 tLZ/tLZ	Part of exon 1 replaced by tauLacZ	Germ-line	Lean (Runty)	Energy expenditure ↑ Adipose beging ↑	*Food intake↓	Smemo et al., 2014
Irx3 Δ/Δ	CRISPR/Cas9 editing of exon 2	Germ-line	Lean	Adipose beging ↑	Sucrose preference↓	Sobreira et al., 2021
Irx5 eGFP/eGFP	Part of exon 1 replaced by eGFP	Germ-line	Lean (Runty)	Energy expenditure ↑ Adipose beging ↑	*Food intake↓	Bjune et al., 2018; Son et al., 2021b
Irx3+Irx5+ /Irx3 del Irx5 eGFP	Deletion of exons 2 to 4 of Irx3 in Irx5eGFP line	Germ-line	Lean	Energy expenditure ↑ Adipose beging ↑	Food intake↓ Hypothalamic leptin response ↑	Son et al., 2021a
Irx5 Δ/+	CRISPR/Cas9 editing of exon 2	Germ-line	Lean	Adipose beging ↑	N/A	Sobreira et al., 2021
Ins2-Cre;Rosa26EnR–Irx3/+	Expression of dominant-negative form of IRX3	Hypothalamus	Lean	Energy expenditure ↑ Adipose beging ↑	*Food intake↓	Smemo et al., 2014; Son et al., 2021b
Ins2-Cre;Irx3F/F	Flanking exons 2 to 4 with loxP sites	Hypothalamus	Lean	No difference in energy expenditure	Food intake↓ Hypothalamic leptin response ↑	Son et al., 2021a

Deletion of Irx3 in macrophage, or expression of a “dominant-negative form of mouse IRX3” in adipose tissue (aP2-Cre;Rosa26^EnR–Irx3/+) or “human IRX3” in brown adipose tissue (Ucp1-Cre;Rosa26^hIRX3/+) leads to a lean phenotype with adipose beiging and elevated energy expenditure (Smemo et al., 2014; Yao et al., 2021; Zhang et al., 2021).

*Though difference in daily food intake is not significantly different, these mutants show reduced amounts of food intake from long-term feeding analysis over life time.