Analysis Tools
mortality/aging
|
• homozygous null mice die at or before birth as a result of severe congenital defects
|
pigmentation
|
• although a bilayered optic cup is formed, a retinal pigmented epithelium fails to develop on the dorsal side
• a pseudostratified neuroepithelial layer resembling neural retina is formed instead of RPE
|
cardiovascular system
|
• three of five embryos showed abnormal aortic arch arteries
|
|
• three of five embryos showed abnormal aortic arch arteries: two had retroesophageal right subclavian artery
|
|
• three of five embryos showed abnormal aortic arch arteries
|
|
• one embryo had type B interrupted aortic arch
|
|
• all five mutant embryos studied (two at E14.5, two at E15.5, and one at full term) showed severe cardiac outflow tract malformations
|
|
• one mutant embryo exhibited persistent truncus arteriosus (PTA) subtype A2: complete failure to septate the outflow tract, with the persisting single vessel originating from the right ventricle through a single valvular apparatus
• the remaining embryo had PTA subtype A1: a fused valvular apparatus was present, but the septated aortic and pulmonary vessels were located distally
|
|
• in three out of five mutant embryos, the aortic and pulmonary outflow structures were normally formed (normal outflow tract septation), but both originated abnormally from the right ventricle
|
|
• most mutant hearts are located within a normal pericardial cavity; in some embryos, no pericardial cavity is detected, although the surface of the heart is lined by epicardium
|
cellular
|
• failure of craniofacial development is accompanied by cell death associated with the trigeminal ganglia at E9.5, and with the face region at E12.5
|
craniofacial
|
• homozygotes lack recognizable ventral craniofacial structures
|
|
• the cranial vault is not distinguishable
|
|
• the mutant mandibles remain unfused
|
|
• the maxilla is not distinguishable
|
|
• although the cochlea is present, middle-ear bones are not observed
|
absent mouth
(
J:33031
)
absent snout
(
J:33031
)
embryo
| N |
• at E8.5, mutant embryos display no gross anatomical abnormalities
|
|
• homozygotes show disrupted development and migration of the dorsolateral body wall that normally generates ventral surface
• mutants do not display a general failure of body wall formation, as the dorsal surface of the torso is covered by mature keratinized skin, containing hair follicles
|
endocrine/exocrine glands
| N |
• mutant fetuses show normal norepinephrine and dopamine levels as well as normal dopa decarboxylase actvity in the adrenal and kidney
|
|
• relative to wild-type fetuses, mutant fetuses display a 66% reduction of adrenal phenylethanolamine N-methyltransferase (PNMT) activity, and a >50% decrease in adrenal epinephrine
• in the kidney, PNMT activity is reduced by 36% and kidney epinephrine is decreased by >70%
|
growth/size/body
|
• mutants exhibit thoracoabdominoschisis: the ventral body wall is absent, and abdominal and thoracic contents are exposed
|
|
• by E12.5, the mutant mouse head is largely neurepithelium
|
absent mouth
(
J:33031
)
absent snout
(
J:33031
)
|
• all homozygotes are runted, consistent with hypoplastic and retarded development of several tissues and organs, including the heart and kidney
|
hearing/vestibular/ear
|
• although the cochlea is present, middle-ear bones are not observed
|
|
• the tympanic ring is absent
|
limbs/digits/tail
absent radius
(
J:33031
)
|
• several mutants display forelimb defects: 18 of 28 mutant embryo forelimbs lacked a radius
|
skeleton
| N |
• the axis and atlas appear normal
• the exoccipital, basioccipital and basisphenoid bones of the chordal skeleton are identifiable
|
|
• homozygotes lack recognizable ventral craniofacial structures
|
|
• the cranial vault is not distinguishable
|
|
• the mutant mandibles remain unfused
|
|
• the maxilla is not distinguishable
|
|
• although the cochlea is present, middle-ear bones are not observed
|
absent radius
(
J:33031
)
|
• several mutants display forelimb defects: 18 of 28 mutant embryo forelimbs lacked a radius
|
|
• mutant skeletons lack clavicles
|
|
• the mutant rib cage fails to fuse to a central sternum
|
vision/eye
|
• although a bilayered optic cup is formed, a retinal pigmented epithelium fails to develop on the dorsal side
• a pseudostratified neuroepithelial layer resembling neural retina is formed instead of RPE
|
|
• anterior margins of the developing optic cup fail to form an iris and ciliary body
|
|
• mutant embryos display absence of a developing cornea
|
|
• mutant lenses are malformed and remain connected to the overlying ectoderm via a lens stalk
• an anterior lens epithelium fails to develop
|
|
• all mutant embryos which have eyes show abnormal lens induction
• lens induction fails completely in some mutants (33% of E11.5 and 14% of E12.5)
|
|
• the surface ectoderm which normally invaginates to form the lens vesicle is replaced by mesenchymal cells that occupy the inner aspect of the optic cup
• in most mutants (67% of E11.5; 43% of E12.5) the surface ectoderm has been induced to invaginate into the optic cup but lenses appear abnormal
|
small lens
(
J:52402
)
|
• the optic stalk is often mislocated, with the choroidal fissure either delayed or failing to close
|
|
• the optic stalk is often mislocated
|
|
• almost all mutant retinas show absence of a defined ganglion cell layer
|
anophthalmia
(
J:52402
)
|
• at E9.5-E10.5, homozygotes have eyes on the surface of their head; however, all mutants examined at E12.5 and later fail to exhibit eyes
• 38% of mutant embryos completely lack either one or both eyes
• 62% of mutants have eyes or eye rudiments that are embedded inside the head and appear to be surrounded by an outgrowth of mesenchymal and neural tissue
|
nervous system
anencephaly
(
J:33031
)
exencephaly
(
J:33031
)
|
• at E9.5, the cranial neural folds remain widely separated, resulting in exencephaly
• closure of the spinal neural tube is normal
|
|
• at E10.5, the trigeminal ganglion (V) is greatly reduced relative to wild-type; in contrast, the dorsal root ganglia appear normal
|
|
• the morphologies of the VII/VIII ganglion complex, and IX and X ganglia and nerves, are disrupted with variable penetrance
|
|
• at E10.5, the oculomotor nerve is not observed
|
