Table 1.

Circadian Gene Knockout Mice and Their Metabolic Phenotypes^a

Mouse Strain, Background, and Age	Diet	Glucose and GTT	Insulin and ITT	Serum TG	Body Weight and Adiposity	Liver Phenotype	Refs
Rev-erba KO + sh Rev-erbb (Vennstrom; backcrossed to B6)	NC	Mild hypoglycemia				Hepatic steatosis	[103]
Rev-erbα/β tamoxifen-inducible double KO (Cho)	NC	Fasting hyperglycemia					[37]
Rev-erbα KO (Schibler; backcrossed to B6)	NC	Hyperglycemia Normal GTT	Mild hyperinsulinemia Normal ITT		Normal Increased adiposity	Higher hepatic TG	[104]
	HFD (53%)	Hyperglycemia	Hyperinsulinemia		Increased DIO	Higher hepatic TG
Per1/2 (129)	NC	Impaired GTT	Enhanced insulin sensitivity		Similar to control		[105]
Per1/2	NC					Lower hepatic TG	[32]
Per2ldc	NC			Elevated	Reduced (>4 months) Reduced adiposity		[106]
Per2Brdm1	NC	Hypoglycemia					[107]
Per2Brdm1 (B6)	NC	Higher glucose clearance	Elevated Enhanced insulin sensitivity				[108]
Per2Brdm1 (29S5/B6-Tyrc-Brd)	NC	Fasting hypoglycemia Normal GTT	Normal		Normal Reduced adiposity		[109]
Cry1/2 double KO (Sancar)	NC	Normal fasting glucose Impaired GTT	Fasting hypoinsulinemia		Leaner		[110]
Cry1/2 double KO (Sancar)	NC	Normal fasting glucose Impaired GTT	Normal ITT				[111]
Cry1/2 double KO (van der Horst)	NC	Fasting hyperglycemia	Normal insulin		Leaner		[112]
	HFD (45%)	Impaired GTT	Hyperinsulinemia Impaired ITT		Increased DIO	Hepatic steatosis
Bmal1 KO (mixed B6×129)	NC	Normoglycemia loss of diurnal rhythm	Enhanced insulin sensitivity	Elevated			[35]
Bmal1 KO (mixed B6×129; Bradfield; 8–12 weeks)	NC	Normal fasting glucose Impaired GTT	Hypoinsulinemia Insulin hypersensitivity		Similar to control Increased adiposity		[105]
Liver–Bmal1 KO (mixed B6×129; Weitz; albumin–Cre)	NC	Fasting hypoglycemia Higher glucose clearance	Normal		Normal
Pancreas–Bmal1 KO (mixed B6×129×ICR; Bradfield; PDX1–Cre)	NC	Hyperglycemia Impaired GTT	Hypoinsulinemia		Normal		[36]
Bmal1 KO(B6; Saito)	NC			Elevated	Leaner		[113]
	HFD (60%)			Elevated	Protected from DIO Ectopic fat accumulation	Hepatic steatosis	[113]
Adipose–Bmal1 KO	NC		Normal		Elevated in AP2–Cre model		[114]
(B6; Bradfield; AP2–Cre and adiponectin–Cre)	HFD				Increased DIO in both models
Bmal1 KO (backcrossed to B6; Bradfield, 4–12 weeks)	NC	Fasting hyperglycemia	Loss of diurnal insulin sensitivity				[115]
	HFD (60%)				Similar to control Increased adiposity
Bmal1 KO (mixed B6×129; Bradfield)	NC	Normal fasting glucose Normal GTT	Hypoinsulinemia Normal ITT	Elevated	Slightly lower Increased adiposity		[116]
	HFD (22%)		Normal	Elevated	Similar to control Increased adiposity
Bmal1	NC	Fasting hyperglycemia					[79]
ClockΔ19 (B6)	NC		Enhanced insulin sensitivity				[35]
	HFD (45%)		Protected from insulin intolerance		Similar to control
ClockΔ19 (B6)	NC	Hyperglycemia	Normal	Elevated	Higher Increased adiposity	Hepatic steatosis	[117]
	HFD (45%)				Higher Increased adiposity
ClockΔ19 (ICR)	NC	Normoglycemia	Normal	Reduced	Similar to control		[118]
	HFD (32%)		Hypoinsulinemia		Protected from DIO
ClockΔ19	NC				Normal	Normal	[119]
(ICR)	HFD				Similar to control	Lower hepatic TG
ClockΔ19+MEL (CBA; 6 months)	NC	Normoglycemia Impaired GTT	Hypoinsulinemia Insulin hypersensitivity	Reduced	Normal		[120]
ClockΔ19 (B6; 8 months)	NC	Fasting hyperglycemia Impaired GTT	Hypoinsulinemia Normal ITT and islet dysfunction				[36]
ClockΔ19 (B6)	NC				Higher Increased adiposity		[121]

^aAbbreviations: AP2, adipocyte fatty acid binding protein (FABP4); GTT, glucose tolerance test; HFD, high-fat diet (with % fat); ITT, insulin tolerance test; KO, knockout; NC, normal chow; TG, triglyceride.