The Circadian Clock in Cancer Development and Therapy - Progress in Molecular Biology and Translational Science - page 237

Table 9.2 Phenotypes of circadian gene-mutant mouse models
Circadian
genes

Circadian behavior
phenotypes

Mouse models Disease phenotype Key targets affected References

Bmal1 Bmal1 -

heterozygous

Normal Premature aging and cancer

prone

N/A 29

Bmal1 -null Arrhythmic Premature aging, metabolic

syndrome, immune deficiency,
caner prone, deregulated drug
response

CDC2, Cyclin B1, Cyclin D1,
Cyclin E, p21 WAF1/CIP1 ,
p16 Ink4a , p53, RB, and WEE1

23, 29, 124,
125, 149, 166,
168, 169,
180-182

Keratinocyte-
specific Bmal1 -
null

Normal Hyperproliferation and

deregulated UVB DNA damage
to hair cells at a young age

DAB2, DKK3, LEF1,
p16 Ink4A , SMAD3, TGFBR2,
and WNT10a

22

CD34 þ and Integrin- a 6 Keratinocyte-

specific Bmal1 /
oncogenic Sos

Normal Resistance to cutaneous

squamous tumors, senescence of
hair cells at 10 months of age

167

Macrophage-
specific Bmal1 -
null

Normal Immune deficiency IL-6 183

Clock Clock -mutant

( Clock D 19)

Lengthened period
and arrhythmic in
constant darkness

Metabolic syndrome, premature
aging, and deregulated drug
response

AKT1, ATR1, Cdk2, Chk1,
Chk2, Cyclin D3, Cyclin E1,
EGF, ER a ,JAK2,
p21 WAF1/CPI1 ,p27 KIP1 ,
PBEF, TGF b ,andWEE1

19, 129, 163,
166, 181,
184-187

Clock -null Shortened period

and failure of phase
delay/advance

Premature aging and immune
deficiency

NF- k B and WEE1 162, 164