Analysis Tools
mortality/aging
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• a little less than half die by weaning with 85% of those deaths occuring within 24 hours of birth
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• Background Sensitivity: a little less than half die by weaning
• some mice survive to adulthood and are fertile; however, survivors display limited growth and delayed eye opening
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skeleton
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• the cricoid is always larger than the thyroid cartilage due to fusion with the first tracheal rings
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• the cricoid cartilage is fused with the first tracheal rings
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• tracheal rings do not display a normal banding pattern
• the cartilage does not not extend as dorsally as in wild-type
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respiratory system
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• disorganized larynx morphology
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• the cricoid is always larger than the thyroid cartilage due to fusion with the first tracheal rings
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• reduced branching of the bronchial tree associated with disorganization of the surrounding mesenchyme
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• at E15.5, the number of bronchioli per area scored is reduced by 33%
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• thickened alveolar walls at the saccular stage (E17.5-E18.5)
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• cellular disorganization in the bronchial epithelial lining and underlying lamina propria
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• at E15.5, the number of terminal acini per area scored is reduced by 33%
• the diameter of terminal acini is generally reduced in size
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atelectasis
(
J:45341
)
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• high proportion of collapsed lungs at autopsy
• at birth, fluid-filled bronchioli and alveoli are observed
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• at E15.5, the diameter of bronchioli is generally reduced in size
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• cellular disorganization in the bronchiolar epithelial lining and underlying lamina propria
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• disorganized tracheal epithelium and adjacent submucosa and thickened lamina propria, with variable expressivity
• tracheal epithelium appears to be stratified rather than pseudostratified
• wider lamina propria along the entire length of trachea
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• tracheal rings do not display a normal banding pattern
• the cartilage does not not extend as dorsally as in wild-type
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• the cricoid cartilage is fused with the first tracheal rings
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• tracheal occlusion in severely affected mice
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• narrowing of the trachea with severe reduction in the lumen diameter
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• most pups display respiratory disterss immediately after birth
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• reduced levels of pulmonary surfactant proteins
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digestive/alimentary system
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• delayed maturation of the secretion pattern of digestive enzymes for disaccharides
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vision/eye
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• in mice surviving to adulthood
(J:45341)
• by about 7 days
(J:84449)
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hearing/vestibular/ear
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• delayed ear elevation by approximately 1.5 days
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growth/size/body
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• delayed ear elevation by approximately 1.5 days
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ovary cyst
(
J:182519
)
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• at 10 months of age, 5 of 8 ovaries from nulliparous female homozygotes contain large fluid-filled epithelial cysts; in contrast, only two small cysts are detected in 1of 5 control ovaries
• immunolabeling studies suggest that these ovarian epithelial inclusion cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas
• staining by ovarian cancer markers supports the notion that these cysts may represent preneoplastic lesions
• at 10 months of age, estrous acyclicity and presence of ovarian epithelial cysts correlate with a reduced expression of specific EGFR signaling components
• however, 4- and 10-month-old nulliparous females exhibit normal ovarian folliculogenesis at diestrus
• similarly, ovarian histology of pregnant female homozygotes is normal
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• in mice surviving to adulthood
(J:45341)
• between 13 and 35 days after birth
(J:84449)
• size differential decreases after 5 weeks of age and is only 2% by age 84 days
(J:84449)
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endocrine/exocrine glands
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• thyroid follicles slightly disorganized at E16.5
• large proportion of empty or incompletely filled follicles at E17.5-E18.5
• thyroid normal at birth through 30 days of age but follicle diameter decreased 15% at 30 days of age
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ovary cyst
(
J:182519
)
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• at 10 months of age, 5 of 8 ovaries from nulliparous female homozygotes contain large fluid-filled epithelial cysts; in contrast, only two small cysts are detected in 1of 5 control ovaries
• immunolabeling studies suggest that these ovarian epithelial inclusion cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas
• staining by ovarian cancer markers supports the notion that these cysts may represent preneoplastic lesions
• at 10 months of age, estrous acyclicity and presence of ovarian epithelial cysts correlate with a reduced expression of specific EGFR signaling components
• however, 4- and 10-month-old nulliparous females exhibit normal ovarian folliculogenesis at diestrus
• similarly, ovarian histology of pregnant female homozygotes is normal
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homeostasis/metabolism
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• at 10 months of age, nulliparous females exhibit a 2-fold increase in serum 17beta-estradiol concentrations at estrus relative to wild-type controls
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• elevated TSH levels at 15 days of age but not at 17 days
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craniofacial
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• delayed ear elevation by approximately 1.5 days
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reproductive system
ovary cyst
(
J:182519
)
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• at 10 months of age, 5 of 8 ovaries from nulliparous female homozygotes contain large fluid-filled epithelial cysts; in contrast, only two small cysts are detected in 1of 5 control ovaries
• immunolabeling studies suggest that these ovarian epithelial inclusion cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas
• staining by ovarian cancer markers supports the notion that these cysts may represent preneoplastic lesions
• at 10 months of age, estrous acyclicity and presence of ovarian epithelial cysts correlate with a reduced expression of specific EGFR signaling components
• however, 4- and 10-month-old nulliparous females exhibit normal ovarian folliculogenesis at diestrus
• similarly, ovarian histology of pregnant female homozygotes is normal
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• nulliparous females display precocious puberty, with the first estrus observed earlier (day 31.9) relative to wild-type controls (day 34.4)
• notably, vaginal opening occurs at similar ages for mutant and control females
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• nulliparous female homozygotes display an early onset of estrous acyclicity
• starting at 4.5-6 months of age, nulliparous females show a significant decrease in the number of cycles per month with a lengthened diestrus period
• by 8-10 months of age, nulliparous females show prolonged diestrus and metestrus periods with a reduced estrus duration leading to a further decrease in the number of estruses per month
• however, at 8-10 months of age, all female homozygotes are fertile with a mean litter size that is comparable to that of wild-type controls
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• starting at 4.5-6 months of age
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short estrus
(
J:182519
)
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• by 8-10 months of age
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• by 8-10 months of age
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• nulliparous females show a prolonged estrous cycle with increased metestrus-diestrus length that worsens with age
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