Mouse Genome Informatics
hm1
    Bbs4Gt1Nk/Bbs4Gt1Nk
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• some outer hair cell stereociliary hair bundles are misoriented or have a flattened shape

growth/size/body
• 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
• statistically smaller than litter mates at 2 weeks of age
• females remain underweight until about 10 weeks
• males remain underweight until 12 weeks of age

adipose tissue
• increased abdominal fat

liver/biliary system
• in males
• fat accumulation in the livers of obese mice

homeostasis/metabolism
• elevated total and insoluble bilirubin in males
• increased ratio of total cholesterol to HDL cholesterol
• positive correlation between between body weight and HDL-cholesterol
• elevated levels of alanine aminotransferase and aspartate aminotransferase
• increased alkaline phosphatase in females only
• increased creatine kinase

immune system
• increased globulin levels

vision/eye
• retinas normal at 4 months but distinctly abnormal at 10 months
• 80% with retinal abnormalities by 11 months
• large atrophic lacunae
• confluent pigment migration
• gross pigmentary retinopathy
• thinned
• loss of nuclei
• photoreceptors appear as a single sparse layer of nuclei by 28 weeks of age
• 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
• 4 week cone function b wave is 12% normal, 7% at 8 weeks and at 14 weeks

behavior/neurological
• less socially aggressive
• less rearing activity in open field tests
• more time spent in dark box and fewer transitions to light

nervous system
• neural tube defects in 14% of embryos result in midbrain exencephaly
• some outer hair cell stereociliary hair bundles are misoriented or have a flattened shape

reproductive system
• in one of 22 females (J:134093)

cardiovascular system

pigmentation
• confluent pigment migration
• gross pigmentary retinopathy

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

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

hematopoietic system
• increased globulin levels

Mouse Models of Human Disease
OMIM IDRef(s)
Bardet-Biedl Syndrome 4; BBS4 615982 J:134093


Mouse Genome Informatics
hm2
    Bbs4Gt1Nk/Bbs4Gt1Nk
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 40-50% embryonic lethality is seen at E10.5

growth/size/body
• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type
• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice
• all homozygotes are runts at birth, however no mutants display polydactyly, situs inversus, or renal or liver abnormalities unlike humans with BBS mutations
• by 10 weeks of age 10% of homozygotes are obese

taste/olfaction
• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type
• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice
• olfactory epithelium shows little of no response to a wide variety of odorants

vision/eye
• 30% of homozygotes develop retinal degeneration

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

respiratory system
• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type
• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

craniofacial
• olfactory cilia lack stable microtubules and the ciliary layer is thinner compared to wild-type
• the apical dendrites are distorted rather than projecting straight to the surface as in wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Bardet-Biedl Syndrome 4; BBS4 615982 J:92950
Obesity 601665 J:92950