Phenotypes Associated with This Genotype

Genotype
MGI:6471957

• Allelic Composition: Bbs2^tm1.1Huss/Bbs2^tm1.1Huss
• Genetic Background: involves: 129S6/SvEv * C57BL/6

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

adipose tissue

increased total body fat amount ( J:296033 )

• body fat content is higher in 2 and 3 month old mice

• treatment with the brain-penetrant glucosylceramide synthase inhibitor Genz-667161 attenuates the weight and body fat differences up to 6 months of age

increased fat cell size ( J:296033 )

• adipocytes exhibit greater heterogeneity and are larger

• Genz-667161 treatment normalizes adipocyte size

behavior/neurological

polyphagia ( J:296033 )

• mice are hyperphagic

• Genz-667161 treatment reduces food consumption

cellular

abnormal primary cilium morphology ( J:296033 )

• loss of hypothalamic primary cilia

• Genz-667161 treatment reduces the loss of hypothalamic cilia

abnormal olfactory epithelium cilium morphology ( J:296033 )

• mice exhibit reduced cilia in the main olfactory epithelium

craniofacial

abnormal olfactory epithelium morphology ( J:296033 )

• mice show an accumulation of Dcx+ immature neurons at the expense of OMP+ mature neurons in the main olfactory epithelium

• Genz-667161 treatment preserves the cellular composition of the main olfactory epithelium

abnormal olfactory epithelium cilium morphology ( J:296033 )

• mice exhibit reduced cilia in the main olfactory epithelium

growth/size/body

abnormal olfactory epithelium morphology ( J:296033 )

• mice show an accumulation of Dcx+ immature neurons at the expense of OMP+ mature neurons in the main olfactory epithelium

• Genz-667161 treatment preserves the cellular composition of the main olfactory epithelium

abnormal olfactory epithelium cilium morphology ( J:296033 )

• mice exhibit reduced cilia in the main olfactory epithelium

decreased birth body size ( J:296033 )

• mice are smaller at birth but the difference is no longer seen at 2 months of age

obese ( J:296033 )

• 3 month old mice are heavier and develop obesity

• treatment with Genz-667161 attenuates the weight and body fat differences up to 6 months of age

increased liver weight ( J:296033 )

• increase in liver weight

• Genz-667161 treatment normalizes liver weight

homeostasis/metabolism

increased circulating leptin level ( J:296033 )

• increase in serum leptin levels

• Genz-667161 treatment reduces serum leptin levels

increased circulating triglyceride level ( J:296033 )

• triglyceride levels are significantly increased albeit within normal range

• Genz-667161 treatment reduces triglyceride levels to wild-type levels

increased circulating alanine transaminase level ( J:296033 )

• serum alanine transaminase levels are significantly increased albeit within normal range

• Genz-667161 treatment reduces serum alanine transaminase levels to wild-type levels

increased ceramide level ( J:296033 )

• mice show increased glucosylceramide levels in serum

• Genz-667161 treatment reduces levels of glucosylceramide in the serum

liver/biliary system

increased liver weight ( J:296033 )

• increase in liver weight

• Genz-667161 treatment normalizes liver weight

nervous system

decreased retina cone cell number ( J:296033 )

decreased retina rod cell number ( J:296033 )

respiratory system

abnormal olfactory epithelium morphology ( J:296033 )

• mice show an accumulation of Dcx+ immature neurons at the expense of OMP+ mature neurons in the main olfactory epithelium

• Genz-667161 treatment preserves the cellular composition of the main olfactory epithelium

abnormal olfactory epithelium cilium morphology ( J:296033 )

• mice exhibit reduced cilia in the main olfactory epithelium

taste/olfaction

abnormal olfactory epithelium morphology ( J:296033 )

• mice show an accumulation of Dcx+ immature neurons at the expense of OMP+ mature neurons in the main olfactory epithelium

• Genz-667161 treatment preserves the cellular composition of the main olfactory epithelium

abnormal olfactory epithelium cilium morphology ( J:296033 )

• mice exhibit reduced cilia in the main olfactory epithelium

anosmia ( J:296033 )

• mice exhibit up to a 5-fold increase in latency time to find a buried treat indicating anosmia

• Genz-667161 treatment corrects the anosmia

vision/eye

decreased retina cone cell number ( J:296033 )

decreased retina rod cell number ( J:296033 )

thin retina outer nuclear layer ( J:296033 )

• outer nuclear layer is thinner in 4-week old mice with a more pronounced difference at 6 months of age

• Genz-667161 treatment results in an approximate 2-fold increase in the thickness of the outer nuclear layer

retina outer nuclear layer degeneration ( J:296033 )

• mice show early-onset severe degeneration of the outer nuclear layer

renal/urinary system

renal/urinary system phenotype ( J:296033 )

N • mice exhibit normal kidney pathology

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 2		DOID:0110124	OMIM:615981	J:296033