Mouse Genome Informatics
hm
    Cby1tm1Ktkm/Cby1tm1Ktkm
B6.129-Cby1tm1Ktkm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Small size and postnatal lethality of Cby1tm1Ktkm/Cby1tm1Ktkm mice

mortality/aging
• the 7 of 32 mice that survive weaning gain weight and survive longer than 18 months
• most mice die by P25
• however, the 7 of 32 mice that survive weaning gain weight and survive longer than 18 months

reproductive system
• some males are infertile (J:147413)

respiratory system
• sinusitis develops as early as P7 that persists throughout the mouse's lifetime
• in adult lungs, the number of alveoli is significantly reduced relative to that in wild-type controls
• however, no significant differences in alveolar septation are observed
• at P11, mutant lungs display a dramatic reduction in cell proliferation, as revealed by BrdU incorporation assays
• however, no significant differences in apoptosis are observed
• at 10-13 wks of age, the number of alveolar saccules per mm2 is reduced by 33% relative to that in wild-type lungs
• enlarged alveolar airspaces are detected as early as P7 and persist in adult lungs
• however, lung morphology is not significantly altered at E18.5 or P4
• no signs of inflammation, infection or fibrosis are observed up to 18 months of age
• at 10-13 wks of age, the gas-exchange surface area is reduced, as shown by an increased inter-airspace wall distance [mean linear intercept (Lm)] and a reduced percentage of lung parenchymal tissue
• lipid-laden interstitial fibroblasts are often found in adult mutant lungs, unlike in wild-type lungs
• at 10-13 wks of age, the proportion of lung airway lumen to the total lung area is significantly greater than that in wild-type lungs
• at P0, mice exhibit ciliary defects in their nasopharynx and proximal lung airways, partly due to impaired basal body docking to the apical membrane of multiciliated cells (J:147413)
• the adult proximal airway epithelium displays abnormal morphology and disorganization of both ciliated and non-ciliated Clara cells (J:166685)
• non-ciliated Clara cells in the adult airway epithelium show atypical morphology
• the apical protrusions of Clara cells appear more prominent than in wild-type lungs
• adult mice show altered differentiation of alveolar epithelial cell lineages
• type I cells alveolar display a significantly thickened, disorganized morphology
• type II alveolar cells display dramatic changes in morphology with a dark electron-dense appearance
• some type II alveolar cells appear to contain an increased number of lamellar bodies
• ciliated cells in the adult proximal airway epithelium appear poorly differentiated with strikingly fewer ciliary projections
• some basal bodies, from which cilia extend, are positioned distantly from the apical plasma membrane and misoriented
• at P0, mice have fewer cilia in their nasopharynx and proximal lung airways compared to wild-type mice (J:147413)
• a normal ciliary ultrastructure with a 9 + 2 microtubular arrangement and normal outer dynein arms are observed (J:147413)
• ciliated cells in the adult proximal airway epithelium show a significant paucity of motile cilia (J:166685)
• however, the axonemal ultrastructure of existing cilia is normal (J:166685)
• tissue elastance (a reflection of the energy conservation in lung tissues) is substantially increased relative to that in wild-type lungs
• at 10-13 wks of age, lung hysteresivity (a reflection of inhomogeneities and structural changes) is significantly increased
• tissue damping (a reflection of the energy dissipation) is also significantly increased
• unlike wild-type mice, 3 of 4 mice lack mucociliary function with the fourth mouse exhibiting small islands of local mucus movement that were not enough to generate mucociliary transport
• at 10-13 wks of age, mice exhibit abnormal pressure-volume (PV) relationships showing relatively small changes in volume with the same increments in applied transpulmonary pressure both initially and at high pressures
• at 10-13 wks of age, airway resistance is decreased
• at 10-13 wks of age, static compliance (a reflection of elastic recoil at a given pressure) is reduced

immune system
• sinusitis develops as early as P7 that persists throughout the mouse's lifetime
• mice infected with P. aeruginosa exhibit accumulation of mucus and bacterial debris along with severe inflammation and distorted morphology of the sinuses unlike similarly treated wild-type mice
• P. aeruginosa-infected mice develop sinus and middle ear infections and fail to clear bacteria from the sinuses unlike similarly treated wild-type mice
• however, mice successfully clear bacteria from their lungs

hearing/vestibular/ear

adipose tissue

growth/size
• at 2 weeks, mice are runted
• mice that survive weaning exhibit low body mass compared to wild-type mice
• neonatal mice appear grossly normal at birth but fail to gain weight

hematopoietic system
• at 2 weeks
• at 2 weeks

embryogenesis
N
• no left-right patterning defects such as situs inversus are observed, suggesting normal structure and function of motile 9 + 0 cilia in the embryonic node (J:147413)

integument

Mouse Models of Human Disease
OMIM IDRef(s)
Ciliary Dyskinesia, Primary, 1; CILD1 244400 J:147413 , J:166685
Otitis Media, Susceptibility to 166760 J:147413