Phenotypes Associated with This Genotype

Genotype
MGI:3608977

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

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

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