Phenotypes Associated with This Genotype

Genotype
MGI:3767679

• Allelic Composition: Bbs1^tm1Vcs/Bbs1^tm1Vcs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

Sperm flagella loss and photoreceptor defects in Bbs1^tm1Vcs/Bbs1^tm1Vcs mice

mortality/aging

mortality/aging ( J:128532 )

N • unlike Bbs2, Bbs4, or Mkks homozygous null mice, no embryonic or neonatal lethality is seen

reproductive system

absent sperm flagellum ( J:128532 )

♂ • sperm lack flagella

male infertility ( J:128532 )

♂

nervous system

nervous system phenotype ( J:194096 )

N • motile cilia in the lateral ventricles are normal

abnormal ependyma motile cilium morphology ( J:128532 )

• ependymal cell cilia are either abnormally long (20%) or have swollen distal regions containing vesicular aggregates (80%)

increased neuron apoptosis ( J:194096 )

• 2-fold in the periventricular region at P3 and P7

abnormal neuronal precursor proliferation ( J:194096 )

• 50% less in the periventricular region at P3 and P7

• neuronal precursor cells are insensitive to PDGF-alpha treatment

• however, lithium therapy rescues increased proliferation

hydrocephaly ( J:194096 )

• non-obstructive

• however, lithium therapy rescues hydrocephalus

enlarged lateral ventricles ( J:128532 )

• ventriculomegaly restricted to the lateral and third cerebral ventricles

• enlargement of the lateral ventricles can be detected by 3 weeks of age and increases with age

• enlargement of the lateral ventricles is more severe than that of the third ventricle

enlarged third ventricle ( J:128532 )

• ventriculomegaly restricted to the lateral and third cerebral ventricles

• enlargement of the lateral ventricles is more severe than that of the third ventricle

dilated brain ventricle ( J:194096 )

• dilated

dilated lateral ventricle ( J:194096 )

• begins between P0 and P3

decreased striatum size ( J:128532 )

• reduction in size of the corpus striatum at 3-weeks and 3.5- to 6-months of age

small hippocampus ( J:128532 )

• reduced in size at 3.5- to 6-months of age

thin cerebral cortex ( J:128532 )

• thinning of the caudal half detected at 3.5- to 6-months of age

abnormal retina photoreceptor morphology ( J:128532 )

disorganized photoreceptor inner segment ( J:128532 )

• significant degeneration is seen at 6 months of age

• severe disruption and disorientation of outer segment membranous discs is seen

photoreceptor inner segment degeneration ( J:128532 )

• significant degeneration is seen at 6 months of age

abnormal photoreceptor outer segment morphology ( J:226512 )

• at P21, retinas show protein mislocalization with a striking accumulation of Stx3 and Stxbp1 as well as loss of polarized Prom1 localization in the OS, similar to retinas in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes

• at P45, the lamellar structure of the OS is severely disrupted; abnormal vesicle formation and longitudinally oriented discs are observed similar to those in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes

disorganized photoreceptor outer segment ( J:226512 )

• at P45, the OS structure is disorganized

vision/eye

abnormal retina photoreceptor morphology ( J:128532 )

disorganized photoreceptor inner segment ( J:128532 )

• significant degeneration is seen at 6 months of age

• severe disruption and disorientation of outer segment membranous discs is seen

photoreceptor inner segment degeneration ( J:128532 )

• significant degeneration is seen at 6 months of age

abnormal photoreceptor outer segment morphology ( J:226512 )

• at P21, retinas show protein mislocalization with a striking accumulation of Stx3 and Stxbp1 as well as loss of polarized Prom1 localization in the OS, similar to retinas in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes

• at P45, the lamellar structure of the OS is severely disrupted; abnormal vesicle formation and longitudinally oriented discs are observed similar to those in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes

disorganized photoreceptor outer segment ( J:226512 )

• at P45, the OS structure is disorganized

retina outer nuclear layer degeneration ( J:128532 )

• significant degeneration is seen at 6 months of age

abnormal eye electrophysiology ( J:128532 )

• the c-wave amplitude is significantly reduced although the response is still luminance-graded

abnormal cone electrophysiology ( J:128532 )

• the variance of the photopic b-wave is significantly different compared to controls

abnormal rod electrophysiology ( J:128532 )

• at 11 weeks of age significant attenuation is seen in a- and b-waves at high scotopic luminances

• however, at 11 weeks of age no difference is seen in amplitude or scotopic response at the lowest scotopic luminance

adipose tissue

increased brown adipose tissue amount ( J:128532 )

increased total body fat amount ( J:128532 )

• significant elevation in fat content at 3.5 and 6 months of age

abnormal fat pad morphology ( J:128532 )

• increase in the amount of reproductive, perirenal, and omental fat

taste/olfaction

impaired olfaction ( J:128532 )

• partial anosmia

behavior/neurological

increased food intake ( J:128532 )

decreased aggression towards mice ( J:128532 )

• display a lack of social dominance

decreased locomotor activity ( J:128532 )

growth/size/body

obese ( J:128532 )

homeostasis/metabolism

increased circulating leptin level ( J:128532 )

cardiovascular system

increased heart rate ( J:128532 )

• higher heart rates in 3.5- to 6-month old mice

• however, no significant changes in mean arterial pressure or cardiac size are detected

renal/urinary system

renal/urinary system phenotype ( J:128532 )

N • unlike humans with Bardet-Biedl syndrome, mice do not develop renal cysts

limbs/digits/tail

limbs/digits/tail phenotype ( J:128532 )

N • unlike humans with Bardet-Biedl syndrome, mice do not display polydactyly

cellular

abnormal ependyma motile cilium morphology ( J:128532 )

• ependymal cell cilia are either abnormally long (20%) or have swollen distal regions containing vesicular aggregates (80%)

absent sperm flagellum ( J:128532 )

♂ • sperm lack flagella

increased neuron apoptosis ( J:194096 )

• 2-fold in the periventricular region at P3 and P7

abnormal neuronal precursor proliferation ( J:194096 )

• 50% less in the periventricular region at P3 and P7

• neuronal precursor cells are insensitive to PDGF-alpha treatment

• however, lithium therapy rescues increased proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 1		DOID:0110123	OMIM:209900	J:128532