Phenotypes Associated with This Genotype

Genotype
MGI:2655516

• Allelic Composition: Bmal1^tm1Bra/Bmal1^tm1Bra
• Genetic Background: involves: 129

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

reproductive system

decreased uterus weight ( J:115188 )

♀

prolonged estrous cycle ( J:151819 )

♀ • cycle length is 49% longer

♀ • however, the proportion of time spent in each stage is not different from controls

failure of embryo implantation ( J:151819 )

♀ • in the absence of progesterone treatment no implantation sites are seen

♀ • treatment with progesterone beginning at gestational day 3.5 partially rescues the implantation defect

female infertility ( J:151819 )

♀

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:151819 )

N • no difference is detected in estradiol levels during gestation

decreased circulating progesterone level ( J:151819 )

• levels are lower compared to controls regardless of the time of day on day 3 to day 4 of gestation

abnormal circulating protein level ( J:155089 )

• at zeitgeber time (ZT) 14, mice exhibit decreased plasminogen activator inhibitor-1 (PAI-1) levels compared with wild-type mice

abnormal glucose homeostasis ( J:131694 )

• diurnal variation in glucose levels is disrupted

impaired gluconeogenesis ( J:131694 )

increased insulin sensitivity ( J:131694 )

• profound hypoglycemic response regardless of the time of day

abnormal lipid homeostasis ( J:131694 )

• diurnal variation in triglyceride levels is disrupted

abnormal response to injury ( J:155089 )

• time to thrombotic vascular occlusion (TTVO) subsequent to photochemical injury is shorter than in similarly treated wild-type mice

impaired wound healing ( J:193286 )

• show severe wound healing defects characterized by lack of epithelial coverage and a highly disorganized granulation tissue

• most wounds consist mainly of an inflammatory fibrin clot with hardly any fibroblast or keratinocyte proliferation

behavior/neurological

abnormal locomotor activation ( J:66502 )

• level of wheel-running activity in mutants is >3-fold lower during a light cycle and in constant darkness relative to wild-type mice

arrhythmic circadian behavior persistence ( J:66502 )

• when placed in constant darkness after entrainment to a 12 hour/12 hour light/dark schedule, homozygotes do not express any circadian rhythm or locomotor activity in constant darkness

abnormal circadian behavior phase ( J:66502 )

• when a 6 hour light pulse is administered 22 days after placement in constant darkness, no effect on locomotor behavior in null mice is observed nor are there phase shifts or suppression of activity, whereas wild-type mice show a ~3.5 hour phase delay after a light pulse

• few null mutants begin activity within 0.5 hours of lights-off, and 2/17 do not become active at all, whereas all wild-type and heterozygous mice begin activity within 0.5 hours

• 28% of wheel-running activity of mutants is during the light phase, in contrast to 4.2 or 4.1% during light phase in wild-type or heterozygous mice

vision/eye

vision/eye phenotype ( J:124157 )

N • retinas are indistinguishable in morphology or cellular organization from wild-type littermates

abnormal eye electrophysiology ( J:124157 )

• under dark-adapted conditions, ERG b-wave is abnormal with 30% reduced amplitude relative to wild-type mice; ratio of b-wave to a-wave amplitude is highly significant

• under light-adapted conditions, ERG b-wave amplitude is reduced by 60%

adipose tissue

increased total fat pad weight ( J:115188 )

skeleton

skeleton phenotype ( J:115188 )

N • despite the increase in osteoblast number no increase in bone mass is detected

increased osteoblast cell number ( J:115188 )

increased bone resorption ( J:115188 )

• at 2 months of age