mortality/aging
• mice born alive all died within 8 days of birth
|
• occurs as early as E10
|
growth/size/body
• cleft palates found in about 1/3 of mice
(J:27464)
• usually involves secondary palate but sometimes between the maxillary and frontonasal processes
(J:54535)
• delayed closure of palate sometimes seen
(J:54535)
|
• thin and poorly organized
• no fungiform taste papillae
|
pointed snout
(
J:54535
)
• one day delay in external ear opening
|
• approximately half of embryos between E10 and E17 were smaller than normal
|
• small sized mice tended to die within 3-4 days
|
weight loss
(
J:27464
)
• pups of normal size at birth start to loose weight after four days
|
• approximately half of mice between E10 and E17 were smaller than normal
|
digestive/alimentary system
• cleft palates found in about 1/3 of mice
(J:27464)
• usually involves secondary palate but sometimes between the maxillary and frontonasal processes
(J:54535)
• delayed closure of palate sometimes seen
(J:54535)
|
• thin and poorly organized
• no fungiform taste papillae
|
• slow cell proliferation
|
• 2 day old mice with milk in their stomachs but with haemorrhagic and distended intestine
• intestines less developed with fewer and shorter villi
|
• reduction in terminal buds of submandibular glands
|
• undernourished by day 7 and stomachs devoid of milk
|
respiratory system
• at E12.5, mutant embryos show defective branching morphogenesis with 34% fewer primordial tubules and significantly less branching than wild-type controls
• at E14.5, sparser bronchial trees with 30% less tubules and abundant interstitial mesenchyme are observed
• at E15.5, less acinar tubules and terminal sac-like structures are formed
• mutant E12.5 lungs branch poorly in vitro
|
• gasping newborns have, on average, one intra-alveolar septum per four alveoli whereas wild-type controls have one septum per two alveoli
• the number of interalveolar septa is 24/unit surface area versus 60/unit surface area in wild-type controls
• the number of alveoli is reduced by 27% resulting in a 52% smaller alveolar volume than in wild-type controls
|
• newborn mice display thinner interstitial tissue than controls
|
• at E15.5, less acinar tubules and terminal sac-like structures are formed
• at E16.5, mutant acini are abnormally dilated relative to those in control lungs
|
• only a few cells in the collapsed alveoli stain positive for surfactant SP-C or SP-A
(J:27464)
• many of the smaller newborns display collapsed alveoli close to the pleural surface
(J:27464)
• newborn mice display areas of collapsed, hemorrhagic and irregularly shaped alveoli with glycogen-containing cells
(J:41158)
• fewer septations, larger alveolar spaces, and thinner interstitial tissue are observed
(J:41158)
|
• many, but not all, mutant type II pneumocytes contain more glycogen storage granules and fewer lamellar bodies than control cells, suggesting epithelial immaturity
|
• many, but not all, mutant type II pneumocytes contain fewer lamellar bodies than control cells
|
atelectasis
(
J:41158
)
• 4 of 4 newborn mice display large atelectatic areas
• the mean air-filled area comprises 42% of total lung area versus 54% in controls
|
• gasping newborns have, on average, one intra-alveolar septum per four alveoli whereas wild-type controls have one septum per two alveoli
• the number of interalveolar septa is 24/unit surface area versus 60/unit surface in wild-type controls
|
• at P4, many of the smaller newborns display thick and hypercellular alveolar septa
(J:27464)
|
• in culture, mutant E12.5 lung explants display only about half of terminal buds relative to wild-type controls
• intensity of immunostaining for SP-C is the same in the presence or the absence of EGF, unlike in wild-type controls where addition of EGF results in doubling of the number and increases the SP-C immunoreactivity in buds and branching ducts
|
• in culture, mutant E12.5 lung explants display irregularly shaped and dilated terminal buds relative to wild-type controls
|
• many of the smaller newborns display dilated terminal bronchi closer to the pleura
(J:27464)
• wide terminal bronchi lined with numerous glycogen-positive red cells are observed
(J:41158)
|
• 4 of 4 newborn mice display large airways close to the pleural surface
|
• 1 of 4 newborn mice display gasping
|
endocrine/exocrine glands
• reduction in terminal buds of submandibular glands
|
• slow cell proliferation
|
• beta cells proliferate more slowly
• delayed appearance in the pancreas
|
• abnormal organization
• failure of cells to migrate to their normal positions in the pancreas
• appear as streaks next to tuctal epithelial cells
|
• about half normal size at E12.5-E16.5
|
vision/eye
• prolapsed lens adhering to the cornea, identifiable by E17
|
• born with eyes open
• eyes closed by second day after birth
|
hearing/vestibular/ear
• one day delay in external ear opening
|
cardiovascular system
craniofacial
• retarded growth and very thin
|
• cleft palates found in about 1/3 of mice
(J:27464)
• usually involves secondary palate but sometimes between the maxillary and frontonasal processes
(J:54535)
• delayed closure of palate sometimes seen
(J:54535)
|
• thin and poorly organized
• no fungiform taste papillae
|
pointed snout
(
J:54535
)
• one day delay in external ear opening
|
skeleton
• retarded growth and very thin
|
embryo
• approximately half of embryos between E10 and E17 were smaller than normal
|
• small embryos had proportionately small placentas
|
integument
• no hair evident when animals die around day 7
|
• few hair follicles
|
• formed by day 2
• nuclear layer only 1 cell layer thick
|
• very prominent
|
• like control animals at E17
|
• skin is thin with hematomas and petechiae
• becomes dry and flaky
|
flaky skin
(
J:27464
)
homeostasis/metabolism