Phenotypes associated with this allele

• Allele Symbol: Bbs4^Gt1Nk
• Allele Name: gene trap 1, Nicholas Katsanis
• Allele ID: MGI:3055492
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bbs4^Gt1Nk/Bbs4^Gt1Nk	B6.129S7-Bbs4^Gt1Nk	MGI:6370045
hm2	Bbs4^Gt1Nk/Bbs4^Gt1Nk	involves: 129S7/SvEvBrd	MGI:3608977
hm3	Bbs4^Gt1Nk/Bbs4^Gt1Nk	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3055585

Genotype
MGI:6370045

hm1

• Allelic Composition: Bbs4^Gt1Nk/Bbs4^Gt1Nk
• Genetic Background: B6.129S7-Bbs4^Gt1Nk

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

behavior/neurological

impaired contextual conditioning behavior ( J:279506 )

♀ • 8 week old females, but not males, show a decrease in the percentage of freezing and an increase in the distance traveled on day 2 after introduction of the paired tone-foot shock stimulus in the contextual fear experiment indicating a reduction in contextual fear memory in females

impaired cued conditioning behavior ( J:279506 )

♂ • 8 week old males, but not females, show a reduction in the percentage of freezing and increased distance traveled during the cued conditioning session with the tone, indicating impaired cued fear memory in males

cellular

enhanced autophagy ( J:279506 )

• marker analysis indicates an increase in autophagy in P1 and P7 brains

• however, no differences in oxidative phosphorylation complex activities are seen indicating tht mitochondrial dysfunction is not a cause of autophagy

homeostasis/metabolism

enhanced autophagy ( J:279506 )

• marker analysis indicates an increase in autophagy in P1 and P7 brains

• however, no differences in oxidative phosphorylation complex activities are seen indicating tht mitochondrial dysfunction is not a cause of autophagy

nervous system

decreased dendritic spine density ( J:279506 )

• progressive decrease in dendritic spine density at P21 and P42, but not at late embryonic stages

• total spine density is reduced by 55% in dentate gyrus granule cells at P42

• total spine density on the basal and apical dendrites of layer V pyramidal neurons is reduced by 55% and 54%, respectively at P42

• total basal and apical spine density of basolateral amygdala neurons is reduced by 23% and 22%, respectively at P42

• total spine count of dentate gyrus neurons is reduced in all spine subtypes except branched spines, however only the density of thin spines is reduced (22%) when the reduction of dendritic length is taken in account

decreased dendritic spine length ( J:279506 )

• reduction in dendritic spine length at E19.5, P21, and P42

• total dendritic length is reduced by 48% in dentate gyrus neurons and by 25% in basal dendrites of layer V cortex neurons at P42

• basolateral amygdala neuron apical and basal dendrites show a length reduction of 14% and 19%, respectively at P42

abnormal miniature excitatory postsynaptic currents ( J:279506 )

• miniature excitatory postsynaptic currents amplitude is increased in dentate gyrus neurons of 3-4 week old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 4		DOID:0110126	OMIM:615982	J:279506

Genotype
MGI:3608977

hm2

• Allelic Composition: Bbs4^Gt1Nk/Bbs4^Gt1Nk
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

perinatal lethality, incomplete penetrance ( J:134093 )

• reduced production of homozygotes in heterozygote matings

• about 10% of all pups die neonatally with 50% of these being homozygotes

• normal ratio of genotypes at E18.5

• no obvious abnormalities in embryos or dead neonates

hearing/vestibular/ear

abnormal orientation of outer hair cell stereociliary bundles ( J:102697 )

• some outer hair cell stereociliary hair bundles are misoriented or have a flattened shape

growth/size/body

kidney cyst ( J:134093 )

• cystic structural changes involving primarily the tubules and occasionally the glomeruli are noted at 6 months of age or later

renal glomerulus cyst ( J:134093 )

• occasional at 6 months of age or later

increased susceptibility to age related obesity ( J:134093 )

• both sexes tend to become obese with age

• females tend to be significantly overweight by 13 weeks of age

• males tend to become significantly overweight by 24 weeks

• 92% of females and 40% of males become obese

• females show a greater divergence from normal weight than do males

• weight increase due to increased fat and fluids rather than lean mass

decreased body size ( J:134093 )

• statistically smaller than litter mates at 2 weeks of age

decreased body weight ( J:134093 )

• females remain underweight until about 10 weeks

• males remain underweight until 12 weeks of age

enlarged liver ( J:134093 )

• in males

adipose tissue

increased abdominal adipose tissue amount ( J:134093 )

• increased abdominal fat

liver/biliary system

abnormal liver morphology ( J:134093 )

enlarged liver ( J:134093 )

• in males

hepatic steatosis ( J:134093 )

• fat accumulation in the livers of obese mice

abnormal liver physiology ( J:134093 )

homeostasis/metabolism

abnormal blood homeostasis ( J:134093 )

increased blood urea nitrogen level ( J:134093 )

increased circulating bilirubin level ( J:134093 )

• elevated total and insoluble bilirubin in males

increased circulating glucose level ( J:134093 )

abnormal circulating hormone level ( J:134093 )

increased circulating insulin level ( J:134093 )

increased circulating leptin level ( J:134093 )

abnormal circulating lipid level ( J:134093 )

increased circulating cholesterol level ( J:134093 )

increased circulating HDL cholesterol level ( J:134093 )

• increased ratio of total cholesterol to HDL cholesterol

• positive correlation between between body weight and HDL-cholesterol

increased circulating LDL cholesterol level ( J:134093 )

increased circulating VLDL cholesterol level ( J:134093 )

abnormal circulating mineral level ( J:134093 )

increased circulating magnesium level ( J:134093 )

increased circulating sodium level ( J:134093 )

increased circulating alanine transaminase level ( J:134093 )

increased circulating alkaline phosphatase level ( J:134093 )

♀

increased circulating aspartate transaminase level ( J:134093 )

increased circulating creatine kinase level ( J:134093 )

increased circulating lactate dehydrogenase level ( J:134093 )

immune system

increased immunoglobulin level ( J:134093 )

• increased globulin levels

vision/eye

abnormal posterior eye segment morphology ( J:134093 )

optic nerve atrophy ( J:134093 )

abnormal ocular fundus morphology ( J:134093 )

• granular fundus

abnormal retina morphology ( J:134093 )

• large atrophic lacunae

• retinas normal at 4 months but distinctly abnormal at 10 months

• 80% with retinal abnormalities by 11 months

abnormal retina vasculature morphology ( J:134093 )

• vascular attenuation

abnormal retina pigment epithelium morphology ( J:134093 )

• confluent pigment migration

• gross pigmentary retinopathy

abnormal retina photoreceptor layer morphology ( J:134093 )

• thinned

• loss of nuclei

• photoreceptors appear as a single sparse layer of nuclei by 28 weeks of age

abnormal photoreceptor inner segment morphology ( J:134093 )

• thinned

abnormal photoreceptor outer segment morphology ( J:134093 )

• thinned

abnormal eye electrophysiology ( J:134093 )

• both rod and cone responses show severe deterioration in electroretinography by 4 weeks

• by 8 weeks, a wave is 22% normal and 17% normal at 14 weeks

• at 4 weeks, scotopic b wave is 58% normal, 42% normal at 8 weeks, and 22% normal at 14 weeks

abnormal cone electrophysiology ( J:134093 )

• 4 week cone function b wave is 12% normal, 7% at 8 weeks and at 14 weeks

behavior/neurological

decreased aggression towards mice ( J:134093 )

• less socially aggressive

increased anxiety-related response ( J:134093 )

• less rearing activity in open field tests

• more time spent in dark box and fewer transitions to light

increased thigmotaxis ( J:134093 )

nervous system

abnormal neural tube morphology ( J:134093 )

• neural tube defects in 14% of embryos result in midbrain exencephaly

abnormal orientation of outer hair cell stereociliary bundles ( J:102697 )

• some outer hair cell stereociliary hair bundles are misoriented or have a flattened shape

abnormal photoreceptor inner segment morphology ( J:134093 )

• thinned

abnormal photoreceptor outer segment morphology ( J:134093 )

• thinned

optic nerve atrophy ( J:134093 )

reproductive system

hydrometrocolpos ( J:134093 )

♀ • in one of 22 females

cardiovascular system

abnormal retina vasculature morphology ( J:134093 )

• vascular attenuation

pigmentation

abnormal retina pigment epithelium morphology ( J:134093 )

• confluent pigment migration

• gross pigmentary retinopathy

embryo

abnormal neural tube morphology ( J:134093 )

• neural tube defects in 14% of embryos result in midbrain exencephaly

renal/urinary system

kidney cyst ( J:134093 )

• cystic structural changes involving primarily the tubules and occasionally the glomeruli are noted at 6 months of age or later

renal glomerulus cyst ( J:134093 )

• occasional at 6 months of age or later

hematopoietic system

increased immunoglobulin level ( J:134093 )

• increased globulin levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 4		DOID:0110126	OMIM:615982	J:134093

Genotype
MGI:3055585

hm3

• Allelic Composition: Bbs4^Gt1Nk/Bbs4^Gt1Nk
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:92950 )

• 40-50% embryonic lethality is seen at E10.5

cellular

abnormal olfactory epithelium cilium morphology ( J:92950 )

• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type

growth/size/body

abnormal olfactory epithelium cilium morphology ( J:92950 )

• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type

abnormal olfactory sensory neuron morphology ( J:92950 )

• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

decreased birth body size ( J:92950 )

• all homozygotes are runts at birth, however no mutants display polydactyly, situs inversus, or renal or liver abnormalities unlike humans with BBS mutations

obese ( J:92950 )

• by 10 weeks of age 10% of homozygotes are obese

taste/olfaction

abnormal olfactory epithelium cilium morphology ( J:92950 )

• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type

abnormal olfactory sensory neuron morphology ( J:92950 )

• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

abnormal olfaction ( J:92950 )

• olfactory epithelium shows little or no response to a wide variety of odorants

vision/eye

retina degeneration ( J:92950 )

• 30% of homozygotes develop retinal degeneration

nervous system

abnormal olfactory sensory neuron morphology ( J:92950 )

• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

respiratory system

abnormal olfactory epithelium cilium morphology ( J:92950 )

• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type

abnormal olfactory sensory neuron morphology ( J:92950 )

• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

craniofacial

abnormal olfactory epithelium cilium morphology ( J:92950 )

• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type

abnormal olfactory sensory neuron morphology ( J:92950 )

• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bardet-Biedl syndrome 4		DOID:0110126	OMIM:615982	J:92950
obesity		DOID:9970	OMIM:601665	J:92950