Phenotypes associated with this allele

• Allele Symbol: Bbs4^tm1Vcs
• Allele Name: targeted mutation 1, Val C Sheffield
• Allele ID: MGI:3045473
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bbs4^tm1Vcs/Bbs4^tm1Vcs	involves: 129S1/Sv * 129X1/SvJ	MGI:3525001
hm2	Bbs4^tm1Vcs/Bbs4^tm1Vcs	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3045547
cx3	Bbs2^tm1Vcs/Bbs2^+ Bbs4^tm1Vcs/Bbs4^+	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)	MGI:3525000

Genotype
MGI:3525001

hm1

• Allelic Composition: Bbs4^tm1Vcs/Bbs4^tm1Vcs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

behavior/neurological

decreased aggression ( J:94467 )

• mutants are more submissive towards other mice compared to wild-type controls

hyporesponsive to tactile stimuli ( J:94467 )

• mutants are less sensitive to touch and are not vocal during handling

abnormal placing response ( J:94467 )

• when lowered towards a wire grid females show less forelimb paddling

decreased grip strength ( J:94467 )

• mutants are unable to grip a wire grid with the hindlimbs when lifted by the tail

endocrine/exocrine glands

decreased salivation ( J:94467 )

• no salivation is seen when mutants bite on a dowel

taste/olfaction

abnormal olfaction ( J:94467 )

• mutants are less able to find hidden food

nervous system

enlarged lateral ventricles ( J:128532 )

• enlarged at 3.5- to 6-months of age

enlarged third ventricle ( J:128532 )

• enlarged at 3.5- to 6-months of age

abnormal basal ganglion morphology ( 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

digestive/alimentary system

decreased salivation ( J:94467 )

• no salivation is seen when mutants bite on a dowel

renal/urinary system

abnormal renal tubule epithelial cell primary cilium morphology ( J:137093 )

• at 3-4 months of age, the average length of mutant renal tubule primary cilia is significantly increased relative to that in wild-type kidneys

• in culture, wild-type renal tubule epithelial cells of mostly of collecting duct origin maintain a constant ciliary length between days 7 and 10, whereas mutant cilia display an initial delay but surpass the length of wild-type cilia by 10 days

• however, no differences in the cellular composition or proportion of cultured ciliated cells are observed

• the microtubule ultrastructure of basal bodies and axonemes of mutant renal tubule primary cilia remains normal

cellular

abnormal renal tubule epithelial cell primary cilium morphology ( J:137093 )

• at 3-4 months of age, the average length of mutant renal tubule primary cilia is significantly increased relative to that in wild-type kidneys

• in culture, wild-type renal tubule epithelial cells of mostly of collecting duct origin maintain a constant ciliary length between days 7 and 10, whereas mutant cilia display an initial delay but surpass the length of wild-type cilia by 10 days

• however, no differences in the cellular composition or proportion of cultured ciliated cells are observed

• the microtubule ultrastructure of basal bodies and axonemes of mutant renal tubule primary cilia remains normal

homeostasis/metabolism

decreased salivation ( J:94467 )

• no salivation is seen when mutants bite on a dowel

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 4		DOID:0110126	OMIM:615982	J:94467

Genotype
MGI:3045547

hm2

• Allelic Composition: Bbs4^tm1Vcs/Bbs4^tm1Vcs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Examination of wild-type and Bbs4^tm1Vcs/Bbs4^tm1Vcs mouse retina

mortality/aging

preweaning lethality, incomplete penetrance ( J:90812 )

• litters contain fewer than expected homozygous mutants

adipose tissue

increased total body fat amount ( J:90812 )

• increased weight gain is associated with an increase in centrally deposited adipose tissue

behavior/neurological

polyphagia ( J:90812 )

• post weaning weight gain is associated with a greater food intake in homozygous mutants compared to wild-type littermates

growth/size/body

decreased birth body size ( J:90812 )

• homozygous mutants are smaller than wild-type mice at birth

decreased body weight ( J:90812 )

• at 3 weeks of age homozygous mutants weigh less than their wild-type littermates

obese ( J:90812 )

• after weaning homozygous mutants gain more weight and become obese

reproductive system

absent sperm flagellum ( J:90812 )

♂ • flagella are absent throughout the seminiferous tubules, even on cells with condensed sperm heads

male infertility ( J:90812 )

♂ • homozygous males fail to sire offspring

vision/eye

increased susceptibility to age-related retinal degeneration ( J:90812 )

• progressive retinal degeneration and increased apoptosis are seen by 6 weeks of age

• by 7 months photoreceptor cells are absent

cellular

absent sperm flagellum ( J:90812 )

♂ • flagella are absent throughout the seminiferous tubules, even on cells with condensed sperm heads

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 4		DOID:0110126	OMIM:615982	J:90812

Genotype
MGI:3525000

cx3

• Allelic Composition: Bbs2^tm1Vcs/Bbs2⁺; Bbs4^tm1Vcs/Bbs4⁺
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)

normal phenotype

no abnormal phenotype detected ( J:94467 )

• double heterozygotes are normal with respect to body weight, BMI, eye electrophysiology, retinal histology, limb development, and fertility