Analysis Tools
mortality/aging
|
• live-born homozygotes respond to mechanical stimulation but generally die within minutes with respiratory distress
(J:41682)
• homozygotes fail to survive beyond 2 hrs due to impaired cardiovascular function
(J:73681)
|
|
• two-thirds of homozygotes die shortly before or during birth and the remaining are born cyanotic
|
cardiovascular system
|
• 1 of 24 (4.2%) of homozygotes display a hypoplastic pulmonary artery
|
|
• overall, 33.3% of homozygotes aged E13.5 to 18.5 display structural abnormalities of the aorta or its branches
• at E11.5-E16.5, increased apoptosis is noted in aortic segments deriving from the fourth arch
|
|
• 2 of 24 (8.3%) of homozygotes display an aberrant right subclavian artery
|
|
• 5 of 24 (20.8%) of homozygotes exhibit hypoplasia of the aortic arch and/or ascending aorta
|
|
• 2 of 24 (8.3%) of homozygotes exhibit interruption of the aortic arch
|
|
• 1 of 24 (4.2%) of homozygotes with a common arterial trunk display interruption of the aortic arch type B
|
|
• at E18.5, homozygotes exhibit a small, thin-walled, hypoplastic ascending aorta
(J:41682)
• 5 of 24 (20.8%) of homozygotes exhibit hypoplasia of the aortic arch and/or ascending aorta
(J:103391)
|
|
• at E18.5, the mutant myocardium is hypercellular and less trabeculated
(J:41682)
• at E18.5, some homozygotes display normal myocardialization of outflow tract cushions; others exhibit absence of myocardialization, with only a small fibrous ridge below the semilunar valves
(J:103391)
|
|
• overall, 87.5% (21 of 24) homozygous mutant embryos aged E13.5 to 18.5 display abnormalities of the heart and great vessels
|
|
• 1 of 24 (4.2%) of homozygotes display a remnant of the right dorsal aorta
|
|
• at E11.5-E16.5, homozygotes display increased apoptosis in the outflow tract relative to wild-type embryos; apoptosis occurs 1 day later (E14.5), and decreases more slowly than normal
|
|
• 1 of 24 (4.2%) of homozygotes display a common arterial trunk with interruption of the aortic arch type B
|
|
• at E13.5, homozygotes exhibit a normal endocardial cushion volume; however, the normal decrease in total endocardial cushion volume observed in older (E15.5) wild-type embryos does not occur
|
|
• in some cases, fusion of the proximal cushions is incomplete
• incomplete fusion of the endocardial cushions results in a small membranous VSD
• an extensive perimembranous inlet VSD is seen in cases in which outflow tract and AV cushions do not meet
|
|
• homozygotes display various degrees of failure of normal remodeling of the primitive heart e.g. overriding tricuspid valve and DORV interfering with final phase of cardiac looping and wedging
|
|
• at E18.5, 3 of 16 homozygotes exhibit DORV
(J:41682)
• 79.2% (19 of 24) of homozygotes exhibit a DORV with different relative positions of the arterial orifices, i.e. posterior (13 of 19), side-by-side (3 of 19), or slightly anterior (3 of 19) to the pulmonary orifice
(J:103391)
• all mutant hearts with DORV display a bilateral muscular conus
(J:103391)
|
|
• at E18.5, both tricuspid and mitral valve are abnormally connected to the left ventricle
(J:41682)
• 8 of 24 (33.3%) of homozygotes display AV valve thickening
(J:103391)
|
|
• 3 of 24 (12.5%) of homozygotes with tricuspid valve thickening show additional thickening of the mitral valve
|
|
• 8 of 24 (33.3%) of homozygotes display thickening of tricuspid valve thickening, with additional thickening of the mitral valve in 3 cases
|
|
• at E18.5, 4 of 16 homozygotes exhibit DILV
|
|
• at E13.5 to E18.5, homozygotes show a variable degree of hypoplasia of tissues deriving from the outflow tract ridges and the septal parts of the AV cushions
|
|
• at E18.5, 1 of 24 (4.2%) of homozygotes display a large primum-type of atrial septal defect; the lower rim of atrial septum is still mesenchymal and has not fused with AV cushions
|
|
• overall, 62.5% (15 of 24) of homozygotes aged E13.5 to 18.5 display defects related to the region of the AV canal and the ventricular inlet segment
|
|
• 1 of 24 (4.2%) of homozygotes display a complete atrioventricular septal defect
|
|
• 6 of 24 (25%) of homozygotes display overriding of tricuspid orifice via a perimembranous inlet VSD
|
|
• at E18.5, 15 of 16 homozygotes show ventricular septum defects
(J:41682)
• 9 of 24 (37.5%) of homozygotes aged E13.5 to E18.5 show a perimembranous inlet VSD associated with overriding of the tricuspid orifice in 6 cases
(J:103391)
• VSD is more closely related to the aortic orifice in cases with a posterior position of the latter
(J:103391)
• in case of a deficient outflow tract septum, the VSD is committed to both arterial orifices
(J:103391)
|
|
• at E18.5, the aortic and pulmonary orifices are both above the right ventricle; both exhibit valve leaflets that are patent
(J:41682)
• 1 of 24 (4.2%) of homozygotes show thickening of the semilunar valve leaflets
(J:103391)
|
|
• in contrast to septal hypoplasia, E18.5 homozygotes show abnormalities of AV and semilunar valve differentiation
• mutant valve leaflets are hyperplastic and retain a thick and cushion-like appearance
• right-sided valves (tricuspid and pulmonary) are more frequently affected than left-sided valves (mitral and aortic)
|
|
• dextroposition of the outflow tract results in a large-outlet VSD due to aberrant position of the outflow tract septum relative to the ventricular septum
|
|
• 1 of 24 (4.2%) of homozygotes show thickening of the aortic valve leaflets
|
|
• 2 of 24 (8.3%) of homozygotes show thickening of the leaflets of the pulmonary valve, with thickening of the aortic valve in one case
|
|
• at E18.5, homozygotes exhibit an enlarged right ventricle
(J:41682)
• at E15.5, the myocardium of the right ventricle appears spongier, probably due to ventricular dilatation
(J:103391)
|
hearing/vestibular/ear
|
• at E18.5, all homozygotes show incomplete canalization of the scala vestibuli
• a wider space between the epithelial ridge and basilar membrane is observed
|
|
• the interdental cells overlying the spiral limbus appear undifferentiated
|
|
• unlike wild-type mice, all homozygotes fail to form the spiral limbus in the basal cochlear turn by E18.5
|
homeostasis/metabolism
endocrine/exocrine glands
|
• at E18.5, 1 of 5 female homozygotes shows adrenal ectopia
|
 |
• at E18.5, 1 of 5 males displays unilateral testicular hypoplasia with absence of an epididymis and vas deferens dysgenesis
|
|
|
• at E18.5, all male homozygotes exhibit testicular ectopia
|
immune system
|
• at E13.5 or later, homozygotes exhibit failure of macrophage invasion into ocular tissues, suggesting impaired removal of vitreous hyaline cells
|
reproductive system
|
|
• at E18.5, 1 of 5 males displays unilateral testicular hypoplasia with absence of an epididymis and vas deferens dysgenesis
|
|
|
• at E18.5, all male homozygotes exhibit testicular ectopia
|
 |
• at E18.5, 2 of 5 female homozygotes display uterine horn ectopia by ventral displacement relative to the kidneys
|
respiratory system
atelectasis
(
J:41682
)
|
• postnatally, all mutant lungs display collapsed terminal and respiratory bronchioles
|
|
• postnatally, all mutant lungs exhibit dilated conducting airways
|
|
• live-born homozygotes exhibit respiratory distress
|
skeleton
|
• at E18.5, all homozygotes exhibit reduced cranial ossification of the frontal, interparietal, parietal and squamosal bones
|
|
• at E18.5, most homozygotes display dysmorphic calvaria
|
|
• at E18.5, all homozygotes display enlarged fontanelles
|
|
• at E18.5, all homozygotes exhibit reduced frontal bones
|
|
• at E18.5, all homozygotes exhibit reduced interparietal bones
|
|
• at E18.5, all homozygotes show a nearly complete agenesis of the occipital bone
|
|
• at E18.5, all homozygotes exhibit reduced parietal bones
|
|
• at E18.5, all homozygotes show a nearly complete agenesis of the alisphenoid bone
|
|
• at E18.5, homozygotes with cleft palate (23%) show absence of the pterygoid process of the basisphenoid bone
|
|
• at E18.5, all homozygotes exhibit reduced temporal bones
|
|
• at E18.5, the masseteric ridge is more prominent and anteriorly and dorsally displaced
|
|
• at E18.5, all mutant mandibles lack an angle
|
|
• at E18.5, the condyloid process is reduced to one-half of wild-type size
|
|
• at E18.5, the coronoid process is reduced to one-half of wild-type size
|
|
• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf
|
retrognathia
(
J:41682
)
|
• at E18.5, most homozygotes display retrognathia
|
|
• newborn homozygotes exhibit spina bifida occulta
• mutant neural arches form but fail to fuse at the midline of the neural tube
• typically, neural arch defects range from the 10th thoracic to the 5th caudal vertebra
|
|
• all newborn homozygotes lack the deltoid tuberosity on the humerus
|
short radius
(
J:41682
)
|
• all newborn homozygotes exhibit a shortened radius
|
|
• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process
|
short ulna
(
J:41682
)
|
• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process
|
|
• all newborn homozygotes lack the third trochanter on the femur
|
|
• at E18.5, homozygotes show ventral curvature of the clavicles
|
|
• at E18.5, 4 of 16 homozygotes display sternum abnormalities, including bifurcation, incomplete manubrium, and vestigial xiphoid process
|
|
• at E18.5, 4 of 16 homozygotes display a vestigial xiphoid process
|
|
• one-third of homozygotes exhibit wavy irregular ribs or fused ribs
|
rib fusion
(
J:41682
)
|
• at E18.5, 2 of 16 homozygotes display rib fusions
|
|
• at E18.5, 15 of 16 homozygotes exhibit rib barreling, resulting in a larger, more rounded pulmonary cavity
|
vision/eye
|
• at E18.5, the mutant iris stroma is underdeveloped
|
|
• at E14.5, a Descemet's membrane fails to form
|
|
• at E13.5-E14.5, the mutant cornea is abnormally thin
|
|
• at E18.5, all homozygotes display reduced corneal stroma thickness (~33% of wild-type)
(J:41682)
• at E13.5-E14.5, the mutant corneal stroma is significantly thinner with fewer keratocytes than wild-type stroma
(J:73681)
• intercellular spacing is reduced due to decreased ECM accumulation (collagen I, lumican, and keratocan) rather than impaired keratocyte proliferation or enhanced keratocyte apoptosis
(J:73681)
|
|
• at E14.5, no endothelium forms in cornea, limbus and trabecular meshworks
• in contrast, corneal epithelium morphology appears unaffected
|
|
• at E14.5-E18.5, the central stroma adheres to the lens capsule
• at E18.5, reduced collagenous matrix accumulation is noted in the extracellular space between stromal keratocytes
|
|
• at E18.5, cells at the posterior stroma fail to form a continuous endothelial cell layer
• no intercellular junctional complex or basal lamella-like structure is observed in the posterior cornea
|
|
• at E13.5-E14.5, the mutant cornea fails to separate from the lens
|
|
• at E14.5, an anterior chamber fails to form
|
|
• at E18.5, all homozygotes contain a hypercellular infusion of vascularized melanocytes, neuronal cells, and mesenchymal cells in the posterior eye chamber
|
|
• at E18.5, remnant capillaries are found between the stroma and lens capsule
|
|
• the mutant neural retina fails to laminate and undergo normal differentiation by E18.5
|
|
• at E18.5, all homozygotes show hyperplasia of both the inner and outer neuroblastic layers of the retina
|
|
• at E18.5, a huge cell mass of hyalocytes and blood cells accumulates in the vitreous
|
nervous system
|
• newborn homozygotes exhibit spina bifida occulta
• mutant neural arches form but fail to fuse at the midline of the neural tube
• typically, neural arch defects range from the 10th thoracic to the 5th caudal vertebra
|
|
• at E18.5, the mutant spiral ganglion abnormally lies close to the sensory epithelium due to absence of the spiral limbus and Rosenthal's canal
|
muscle
|
• at E18.5, the mutant myocardium is hypercellular and less trabeculated
(J:41682)
• at E18.5, some homozygotes display normal myocardialization of outflow tract cushions; others exhibit absence of myocardialization, with only a small fibrous ridge below the semilunar valves
(J:103391)
|
limbs/digits/tail
|
• newborn homozygotes display limb laxity; both fore- and hindlimbs are rotated and extend toward the midline
|
|
• all newborn homozygotes lack the deltoid tuberosity on the humerus
|
short radius
(
J:41682
)
|
• all newborn homozygotes exhibit a shortened radius
|
|
• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process
|
short ulna
(
J:41682
)
|
• all newborn homozygotes exhibit a shortened ulna with a reduced olecranon process
|
|
• all newborn homozygotes lack the third trochanter on the femur
|
growth/size/body
|
• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf
|
|
• at E18.5, 23% of homozygotes display an extensive anteroposterior cleft of the secondary palate, leaving the nasal septa exposed and extending into the soft palate
• no primary palate cleft or cleft lip was ever observed
|
|
• observed at day E18.5, mice show a failure of the palatal shelves to elevate into a horizontal orientation for the process of apposition and fusion
|
|
• E18.5 homozygotes delivered by Cesarean section show a 12% reduction in birth weight
|
craniofacial
|
• at E18.5, all homozygotes exhibit reduced cranial ossification of the frontal, interparietal, parietal and squamosal bones
|
|
• at E18.5, most homozygotes display dysmorphic calvaria
|
|
• at E18.5, all homozygotes display enlarged fontanelles
|
|
• at E18.5, all homozygotes exhibit reduced frontal bones
|
|
• at E18.5, all homozygotes exhibit reduced interparietal bones
|
|
• at E18.5, all homozygotes show a nearly complete agenesis of the occipital bone
|
|
• at E18.5, all homozygotes exhibit reduced parietal bones
|
|
• at E18.5, all homozygotes show a nearly complete agenesis of the alisphenoid bone
|
|
• at E18.5, homozygotes with cleft palate (23%) show absence of the pterygoid process of the basisphenoid bone
|
|
• at E18.5, all homozygotes exhibit reduced temporal bones
|
|
• at E18.5, the masseteric ridge is more prominent and anteriorly and dorsally displaced
|
|
• at E18.5, all mutant mandibles lack an angle
|
|
• at E18.5, the condyloid process is reduced to one-half of wild-type size
|
|
• at E18.5, the coronoid process is reduced to one-half of wild-type size
|
|
• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf
|
retrognathia
(
J:41682
)
|
• at E18.5, most homozygotes display retrognathia
|
|
• at E18.5, 23% of homozygotes display an extensive anteroposterior cleft of the secondary palate, leaving the nasal septa exposed and extending into the soft palate
• no primary palate cleft or cleft lip was ever observed
|
|
• observed at day E18.5, mice show a failure of the palatal shelves to elevate into a horizontal orientation for the process of apposition and fusion
|
renal/urinary system
|
• following tubulogenesis, female homozygotes show renal dysplastic changes, including renal tubule dilatation, degeneration of the tubular epithelium, proteinuria, and enlargement of the renal pelvis
|
|
• when kidneys form in females, tubulogenesis is followed by degeneration of the tubular epithelium
|
|
• at E18.5, 3 of 10 homozygotes show a dilated renal pelvis
|
|
• when kidneys form in females, tubulogenesis is followed by progressive tubule dilatation
|
absent kidney
(
J:41682
)
|
• at E18.5, 1 of 5 homozygotes (females only) shows renal agenesis
|
digestive/alimentary system
|
• at E18.5, homozygotes with cleft palate (23%) show absence of the palatine shelf
|
|
• at E18.5, 23% of homozygotes display an extensive anteroposterior cleft of the secondary palate, leaving the nasal septa exposed and extending into the soft palate
• no primary palate cleft or cleft lip was ever observed
|
|
• observed at day E18.5, mice show a failure of the palatal shelves to elevate into a horizontal orientation for the process of apposition and fusion
|
embryo
|
• newborn homozygotes exhibit spina bifida occulta
• mutant neural arches form but fail to fuse at the midline of the neural tube
• typically, neural arch defects range from the 10th thoracic to the 5th caudal vertebra
|
hematopoietic system
|
• at E13.5 or later, homozygotes exhibit failure of macrophage invasion into ocular tissues, suggesting impaired removal of vitreous hyaline cells
|
