Table 1 Phenotypes of clock gene mutant mice

From: A role for circadian clock in metabolic disease

References	Organ	Gene	Tg mice analyzed	BW	Hyperphagia	Physical activity	Hyperglycemia	Hyperlipidemia	Hypoinsulinemia	Background
Rudic et al.⁸⁶	Systemic	Clock	Clock ^Δ19	Similar	ND	ND	ND	ND	ND	ND
Turek et al.⁴	Systemic	Clock	Clock ^Δ19	Increase	Yes	Reduced	Yes	Yes	Yes	C57BL/6J
Oishi et al.⁵⁰	Systemic	Clock	Clock ^Δ19	Similar^a	Yes	ND	No	No	No^b	Mixed (C57BL/6JxBALB/cxICR)
Marcheva et al.⁵	Systemic	Clock	Clock ^Δ19	ND	ND	ND	Yes	ND	Yes	C57BL/6J
Doi et al.⁸⁸	Systemic	Clock	Clock ^Δ19	ND	ND	ND	No	ND	No	ICR
Shostak et al.⁶	Systemic	Clock	Clock ^Δ19	Increase	Yes	Normal	ND	No	ND	C57BL/6J
Rudic et al.⁸⁶	Systemic	Bmal1	Bmal1 KO	ND	ND	ND	No	Yes	ND	ND
Lamia et al.³⁹	Systemic	Bmal1	Bmal1 KO	Increase	ND	Normal	Yes	ND	Yes	Mixed (C57BL/6x129)
Kennaway et al.⁷	Systemic	Bmal1	Bmal1 KO	Similar-Lean^c	ND	ND	No	Yes	Yes	Mixed (C57BL/6Jx129/SV)
Kettner et al.⁸	Systemic	Bmal1	Bmal1 KO	Similar-lean^d	ND	ND	ND	ND	ND	C57BL/6J
Nam et al.³⁵	Systemic	Bmal1	Bmal1 KO	Increase	ND	ND	ND	ND	ND	C57BL/6
Grimaldi et al.¹¹	Systemic	Per2	Per2 KO	Lean^e	No	Normal	ND	No^f	ND	129/sv
Yang et al.¹²	Systemic	Per2	Per2 KO	Increase	No^g	ND	ND	ND	ND	C57BL/6J
Zhao et al.¹³	Systemic	Per2	Per2 KO	ND	ND	ND	No^h	ND	No^h	C57BL/6J
Chappuis et al.⁸⁹	Systemic	Per2	Per2 KO	Similar	No	ND	ND	No	ND	Mixed (129S5/C57BL/6-Tyr^c-Brd)
Zani et al.⁹⁰	Systemic	Per2	Per2 KO	Similar	No	ND	Noⁱ	ND.	Yes	Mixed (129S5/C57BL/6-Tyr^c-Brd)
Lamia et al.³⁹	Systemic	Per1/Per2	Per1/Per2 DKO	Lean	ND	ND	Yes	ND	ND	129S1/SvImJ
Kettner et al.⁸	Systemic	Per1/Per2	Per1/Per2 DKO	Increase	No	Normal	ND	ND	ND	C57BL/6J
Lamia et al.¹⁵	Systemic	Cry1	Cry1 KO	ND	ND	Normal	Yes	ND	ND	C57BL/6
Griebel et al.¹⁴	Systemic	Cry1	Cry1 KO	Similar^j	No	ND	No	No	ND	C57BL/6J
Lamia et al.¹⁵	Systemic	Cry2	Cry2 KO	ND	ND	Normal	Yes	ND	ND	C57BL/6
Lamia et al.¹⁵	Systemic	Cry1/Cry2	Cry1/Cry2 DKO	ND.	ND	Normal	Yes	ND	ND	C57BL/6
Barclay et al.⁹⁰	Systemic	Cry1/Cry2	Cry1/Cry2 DKO	Lean^k	No^k	Reduced^l	Yes^m	No	No^m	C57BL/6J
Kettner et al.⁸	Systemic	Cry1/Cry2	Cry1/Cry2 DKO	Lean	No	Reduced	ND	ND	ND	C57BL/6J
Delezie et al.¹²	Systemic	Rev-erbα	Rev-erbα KO	Similarⁿ	No	Normal	Yes	No	No	C57BL/6J
Woldt et al.²⁰	Systemic	Rev-erbα	Rev-erbα KO	ND	ND	Reduced	ND	ND	ND	SV129/OlaHsd
Cho et al.¹⁸	Systemic	Rev-erbα/Rev-erbβ	CAG-CreER Rev-erbα ^fl/fl Rev-erbβ ^fl/fl	ND	ND	Reduced	Yes	Yes^o	ND	C57BL/6
Lamia et al.³⁹	Liver	Bmal1	albumin-cre Bmal1 ^fl/fl	Similar	ND	Normal	No^p	ND	No	Mixed (C57BL/6x129)
Ma X et al.⁴⁰	Liver	Bmal1	albumin-cre Bmal1 ^fl/fl	ND	ND	ND	No^p	ND	ND	Mixed (C57BL/6x129)
Ma D et al.⁴¹	Liver	Bmal1	albumin-cre Bmal1 ^fl/fl	ND	No	ND	ND	Yes	ND	C57BL/6J
Marcheva et al.⁵	Pancreas	Bmal1	Pdx-cre Bmal1 ^fl/fl	Similar	No	Normal	Yes	Yes	Yes	Mixed (C57BL/6x129xICR)
Lee et al.⁴⁹	Pancreas	Bmal1	Rip-cre Bmal1 ^fl/fl	Similar	No	Normal	Yes	ND	Yes	Mixed (C57BL/6JxB6D2)
Paschos et al.²⁷	Adipose	Bmal1	aP2-cre Bmal1 ^fl/fl	Increase	Yes	Normal	Yes	Yes	No	C57BL/6J
Kettner et al.⁸	Adipose	Bmal1	aP2-cre Bmal1 ^fl/fl	ND	ND	ND	ND	ND	ND	C57BL/6J
Westgate et al.⁵⁵	Vessel	Bmal1	Cre ^Tek Bmal1 ^fl/fl	ND	ND	Reduced	ND	ND	ND	C57BL/6J
Dyar et al.⁵⁹	Skeletal muscle	Bmal1	Mlc1f-cre Bmal1 ^fl/fl	Increase	ND	Increase	No	ND	ND	C57BL/6
Dyar et al.⁵⁹	Skeletal muscle	Bmal1	HSA-MerCreMer Bmal1 ^fl/fl	Similar	ND	Normal	No	ND	ND	Mixed (C57BL/6xC3H)
Schroder et al.⁶⁰	Skeletal muscle	Bmal1	HSA-MerCreMer Bmal1 ^fl/fl	ND	No	Normal	ND	ND	ND	Mixed (C57BL/6xC3H)

Abbreviations: DKO, double knockout; KO, knockout; ND, not described; WT, wild type.
All components compared under chow diet at normal physiological condition and response on stress varies between genotypes.
^aClock mutant mice have reduced body weight when fed a high-fat diet.
^bClock mutant mice have reduced insulin level when fed a high-fat diet.
^cMale Bmal1-null mice become mildly lean, but this is not significant in female mice.
^dBmal1 KO mice were similar in body weight compared with their littermates until 12 weeks of age in male and 22 weeks in female, and then steadily shows significant reduction.
^eBmal1 KO group are significantly heavier initially at 3–5 weeks of age, but lose weight from 6 weeks of age, and this becomes significant from 10 weeks of age.
^fBmal1 KO group have low plasma lipid level.
^gPer2 KO group become hyperphagic under a high-fat diet.
^hCirculating insulin is increased and glucose is reduced in the Per2 KO group.
ⁱPer2 KO group have reduced glucose level.
^jCry1 KO group have significant lower body weight when fed a high-fat diet.
^kCry1/Cry2 DKO mice gain weight when fed a high-fat diet. Under a high-fat diet, they eat less compared with WT mice.
^lCry1/Cry2 DKO mice show a trend toward reduced activity in the dark phase both in a chow and high-fat diet, but activity looks increased in the light phase compared with WT mice.
^mCry1/Cry2 DKO mice have high insulin level with systemic glucose intolerance compared with WT mice when fed a high-fat diet.
ⁿRev-erbα KO group gain weight when fed a high-fat diet.
^oTriglyceride is increased but free fatty acid is reduced in the KO group.
^pLiver-specific Bmal1 KO group have reduced glucose level.

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Table 1 Phenotypes of clock gene mutant mice

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