mortality/aging
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• homozygotes die at birth due to absence of the diaphragm muscle and thoracic skeletal defects that could prevent proper breathing
(J:84417)
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muscle
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• homozygotes display impaired primary myogenesis of most body muscles
• at E13.5, all body muscles are either absent or severely disorganized, except some deep back and head muscles
• at E13.5, at the trunk level, the external myogenic layer (cutaneus maximus) is absent while the internal myogenic layer is reduced and disorganized
• most muscles at the shoulder level are absent, the latissimus dorsi is disorganized, and the abdominal and thoracic muscles are severly reduced
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• at E18.5, homozygotes show extensive muscle hypoplasia affecting most of epaxial and hypaxial body muscles, esp. in certain hypaxial muscle groups
• at the distal forelimb level, dorsal muscles are absent and ventral muscles are strongly reduced
• at the distal hindlimb level, most ventral and intermediate muscles are absent, whereas dorsal muscles are only slightly reduced
• some superficial back muscles e.g. the trapezius, the latissimus dorsi and the serratus dorsalis are severely reduced or even absent
• at the head level, only the tongue and related muscles e.g. the genioglossus are markedly reduced
• back intercostal muscles are only slightly reduced
• reduced muscle size is due to a reduced number of myofibers; however, the decrease in the number of myofibers is quite variable in different muscles, ranging from a ~10% reduction in dorsal intercostal muscles to 50% in ventral intercostal muscles, 33% in tibialis anterior and 100% in soleus, plantaris and medial gastrocnemius
• notably, remaining myofibers are properly differentiated into fast and slow types
• in contrast to muscles, the tendons and connective tissue appear to be properly developed
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• at E13.5, homozygotes display a severe reduction and disorganisation of primary myofibers in most body muscles
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• at E18.5, epaxial muscles are slightly reduced
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• although hypaxial progenitors are correctly specified in somites, migrate normally into the limb buds and do not undergo apoptosis, they fail to activate MyoD and myogenin at E11.5
(J:82459)
• at E18.5, hypaxial muscles are severely reduced
(J:84417)
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• at E18.5, the diaphragm muscle is absent
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• at E18.5, the diaphragm is devoid of skeletal muscle fibers and appears as a thin layer of connective tissue
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• at E18.5, back intercostal muscles are present but slightly reduced
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• at E18.5, homozygotes display reduced muscle mass, especially in distal territories
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skeleton
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• at E18.5, homozygotes display severe craniofacial bone abnormalities
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• at E18.5, frontal and nasal bones form an obtuse angle and are not properly aligned
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• at E18.5
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• at E18.5, the styloid process is rudimentary
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• at E18.5, the greater horns of the hyoid bone are rudimentary
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• at E18.5
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short maxilla
(
J:84417
)
|
• at E18.5
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• at E18.5, frontal and nasal bones form an obtuse angle and are not properly aligned
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• at E18.5, the nasal cavity is not reticulated, indicating that chonchae fail to form
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• at E18.5
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• at E18.5, Meckel's cartilage is rudimentary
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• at E18.5, homozygotes show disorganized sternum ossification
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• at E18.5, all homozygotes display variable and asymmetric rib defects, with the right side more strongly affected
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• at E18.5, homozygotes display truncated distal ribs not attached to the sternum
• only 2 of 5 homozygotes show one or two ribs left attached to the sternum
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• at E18.5, homozygotes display rib bifurcations
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rib fusion
(
J:82459
)
|
• at E18.5, homozygotes display fusion of cartilage segments from adjacent ribs
|
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• at E18.5, the atlas and axis are fused
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craniofacial
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• at E18.5, homozygotes display severe craniofacial bone abnormalities
|
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• at E18.5, frontal and nasal bones form an obtuse angle and are not properly aligned
|
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• at E18.5
|
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• at E18.5, the styloid process is rudimentary
|
|
• at E18.5, the greater horns of the hyoid bone are rudimentary
|
|
• at E18.5
|
short maxilla
(
J:84417
)
|
• at E18.5
|
|
• at E18.5, frontal and nasal bones form an obtuse angle and are not properly aligned
|
|
• at E18.5, the nasal cavity is not reticulated, indicating that chonchae fail to form
|
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• at E18.5
|
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• at E18.5, Meckel's cartilage is rudimentary
|
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• at E18.5, homozygotes show a characteristic angle at the nose level between the frontal bone and nasal bone
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• newborns display extensive disorganization of the nasal cavity; no lateral reticulation is observed
• in contrast, the teeth primordium and the vibrissae follicules are correctly developed
|
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• at E18.5, the deep layer of the olfactory epithelium is missing
• in contrast, the surrounding mesenchyme and cartilage appear correctly developed
|
|
• at E18.5, the tongue and related muscles such as the genioglossus are markedly reduced
(J:82459)
• other head muscles e.g the masseter appear correctly developed
(J:82459)
|
digestive/alimentary system
|
• at E18.5, the tongue and related muscles such as the genioglossus are markedly reduced
(J:82459)
• other head muscles e.g the masseter appear correctly developed
(J:82459)
|
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• at E18.5, parotid glands are absent, even though the parotid ducts seem correctly elongated
|
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• at E18.5, submandibular glands are reduced
• however, submandibular gland acini appear histologically normal
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hearing/vestibular/ear
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• at E13.5, BrdU/eosin staining indicates absence of the epithelium in the otic vesicle
|
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• newborns display extensive disorganization of the inner ear
• in contrast, the external and middle ears are correctly shaped
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• at E18.5, the cochlear duct is unrecognizable; only a residual duct is present
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• at E18.5, the semicircular ducts are unrecognizable
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• at E13.5, the otic capsule is strikingly reduced, whereas Rathke's pouch and the trigeminal ganglia (V) and the otic ganglia (IX) are still present
• however, development of the otic vesicle is correctly initiated at E11.5
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hematopoietic system
immune system
renal/urinary system
|
• at E13.5, the metanephros fails to develop whereas the mesonephric duct and the gonads develop correctly
|
absent kidney
(
J:84417
)
|
• at E13.5, homozygotes display renal agenesis, probably due to defects in metanephric blastema differentiation
|
respiratory system
|
• at E18.5, homozygotes show a characteristic angle at the nose level between the frontal bone and nasal bone
|
|
• at E18.5, the nasal cavity is not reticulated, indicating that chonchae fail to form
|
|
• newborns display extensive disorganization of the nasal cavity; no lateral reticulation is observed
• in contrast, the teeth primordium and the vibrissae follicules are correctly developed
|
|
• at E18.5, the deep layer of the olfactory epithelium is missing
• in contrast, the surrounding mesenchyme and cartilage appear correctly developed
|
endocrine/exocrine glands
|
• at E18.5, parotid glands are absent, even though the parotid ducts seem correctly elongated
|
|
• at E18.5, submandibular glands are reduced
• however, submandibular gland acini appear histologically normal
|
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• at E18.5, lacrimal glands are severely disorganized and reduced, and abnormally localized close to the eye, as if the lacrimal ducts fail to elongate posteriorly
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taste/olfaction
|
• at E18.5, histology of the olfactory system is altered
• the olfactive cavity is severely disorganized
|
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• at E18.5, the deep layer of the olfactory epithelium is missing
• in contrast, the surrounding mesenchyme and cartilage appear correctly developed
|
vision/eye
|
• at E18.5, lacrimal glands are severely disorganized and reduced, and abnormally localized close to the eye, as if the lacrimal ducts fail to elongate posteriorly
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embryogenesis
|
• homozygotes show abnormal neural crest development, as shown by defects in formation of Meckel's cartilage, styloid process, and the greater horns of the hyoid bone
|
nervous system
|
• homozygotes show abnormal neural crest development, as shown by defects in formation of Meckel's cartilage, styloid process, and the greater horns of the hyoid bone
|
cellular
|
• at E13.5, BrdU/eosin staining indicates absence of the epithelium in the otic vesicle
|