Analysis Tools
mortality/aging
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• 86% of homozygotes are still alive at E14.5; however, a sharp increase in lethality is noted after E14.5
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• only 49% (95 out of 194) of homozygotes are recovered at birth
• a few attempt, unsuccessfully, to inflate their lungs
• most are still born due to cardio-respiratory failure
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• 12% of homozygous mutant embryos are resorbed at E8.5 (50 out of 57 expected)
• no homozygotes with an abnormal allantois survive past E8.5
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embryo
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• at E10.5, homozygotes show absence of neural crest cell migration through the peripharyngeal region into the proximity of the heart, resulting in lack of outflow tract septation
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• at E8.5, 4 of 50 homozygotes show early ventralization of the mesoderm, with increased extraembryonic mesodermal cells noted in the allantois
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• at E8.5, 4 of 50 homozygotes display a reduced body size
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• at E8.5, 4 of 50 homozygotes display a reduced embryonic region, while the remaining 46 appear morphologically normal
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• at E9.0, the second (hyoid) pharyngeal arch is absent
• in addition, pharyngeal arches three to six fail to form
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• at E8.5, 4 of 50 homozygotes display absence of trunk mesoderm
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• at E8.5, 4 of 50 homozygotes exhibit a significantly hypoplastic and poorly differentiated neural plate
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• at E8.5, 4 of 50 homozygotes display absence of a notochord
• homozygotes that die perinatally show absence of an anterior notochord at E14.5
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• at E9.5, the pharyngeal pouches are reduced to a single swelling in the anterior-most region
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• at E8.5, 4 of 50 homozygotes display absence of somites
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• at E8.5, 4 of 50 homozygotes display an enlarged allantois with an abundance of extraembryonic mesodermal cells
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craniofacial
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• newborn homozygotes display fused basioccipital and basisphenoid bones while the alisphenoid appears normal
• at E14.5, the basioccipital and basisphenoid cartilages are fused; the ossification centre of the basioccipital is narrower and extends into the basisphenoid
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• newborn homozygotes display a hypoplastic presphenoid bone
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• newborn homozygotes lack the squama temporalis
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• newborn homozygotes a smaller temporal bone
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• newborn homozygotes display a shorter zygomatic arch
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• newborn homozygotes exhibit hyoid bone hypoplasia
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• newborn homozygotes lack the coronoid, condylar and angular processes
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• newborn homozygotes lack the angular process
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• newborn homozygotes lack the condylar process
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• newborn homozygotes lack the coronoid process
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• newborn homozygotes display an abnormally small jaw
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• newborn homozygotes lack a secondary palate
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• the palatal shelves fail to extend medially to form the secondary palate
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• at E9.0, the second (hyoid) pharyngeal arch is absent
• in addition, pharyngeal arches three to six fail to form
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• newborn homozygotes have external ears that are set abnormally close to the eyes
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small ears
(
J:83662
)
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• newborn homozygotes exhibit small external ears
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cardiovascular system
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• at E14.5, homozygotes exhibit an enlarged anterior spinal artery
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• in newborns, the pulmonary arteries originate directly from the proximal truncus arteriosus, resulting in the absence of a common pulmonary trunk
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• at birth, part of the aortic arch is absent
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• depending of the laterality of the descending aorta, the right or left subclavian arteries adopt an abnormal retrooesophageal position
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• 40% of newborn homozygotes display an abnormal right-turning aortic arch; the descending aorta is placed on the right side of the esophagus and the left subclavian runs posterior to it
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• absence of the brachiocephalic artery
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• in newborns, the common carotid arteries directly join the truncus arteriosus, resulting in the absence of the brachiocephalic artery and part of the aortic arch
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• at E14.5, homozygotes exhibit persistent truncus arteriosus
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hemorrhage
(
J:83662
)
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• at E14.5, homozygotes exhibit severe hemorrhage
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skeleton
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• newborn homozygotes display fused basioccipital and basisphenoid bones while the alisphenoid appears normal
• at E14.5, the basioccipital and basisphenoid cartilages are fused; the ossification centre of the basioccipital is narrower and extends into the basisphenoid
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• newborn homozygotes display a hypoplastic presphenoid bone
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• newborn homozygotes lack the squama temporalis
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• newborn homozygotes a smaller temporal bone
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• newborn homozygotes display a shorter zygomatic arch
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• newborn homozygotes exhibit hyoid bone hypoplasia
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• newborn homozygotes lack the coronoid, condylar and angular processes
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• newborn homozygotes lack the angular process
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• newborn homozygotes lack the condylar process
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• newborn homozygotes lack the coronoid process
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• newborn homozygotes display an abnormally small jaw
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• newborn homozygotes display reduced laryngeal cartilages
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• newborn homozygotes exhibit cricoid cartilage hypoplasia
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• newborn homozygotes exhibit thyroid cartilage hypoplasia
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• newborn homozygotes lack the anterior arch of the atlas
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• at E14.5, homozygotes display underdeveloped vertebral neural arches
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• newborn homozygotes exhibit reduced vertebral bodies, with delayed ossification and occasional loss of other elements of the vertebrae e.g. spinous processes, neural arches and the anterior arch of the atlas
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hearing/vestibular/ear
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• newborn homozygotes have external ears that are set abnormally close to the eyes
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small ears
(
J:83662
)
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• newborn homozygotes exhibit small external ears
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• at E9.0, otic vesicles are reduced to half their normal diameter
• a conspicuous indentation is noted in the neck region
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• newborn homozygotes display a malformed and reduced otic capsule
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• newborn homozygotes exhibit hypoplasia/absence of the inner ear
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• at E14.5, homozygotes exhibit absence of the Eustachian tube
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• newborn homozygotes display a malformed tympanic ring
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• newborn homozygotes display a reduced tympanic ring
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endocrine/exocrine glands
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• newborn homozygotes lack parathyroid glands (derivatives of pharyngeal pouches 3 and 4)
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• newborn homozygotes lack a thymus (a derivative of the third pharyngeal pouch)
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• newborn homozygotes exhibit a thyroid gland of irregular shape
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• newborn homozygotes display thyroid hypoplasia
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nervous system
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• at E8.5, 4 of 50 homozygotes exhibit a significantly hypoplastic and poorly differentiated neural plate
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• at E9.5, homozygotes display severe cranial sensory ganglia abnormalities, including loss of epibranchial placode-derived ganglia
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• at E9.5, the vestibulocochlear ganglia are deformed and displaced
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• at E9.5, the geniculate ganglion is either extremely reduced or entirely absent
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• at E9.5, the petrosal ganglion is either extremely reduced or entirely absent
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• at E9.5, the petrosal ganglion is either extremely reduced or entirely absent
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• at E9.5, the trigeminal ganglia are deformed and displaced
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• at E9.5, the nodose ganglion is either extremely reduced or entirely absent
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• at E9.5, the nodose ganglion is either extremely reduced or entirely absent
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respiratory system
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• newborn homozygotes display reduced laryngeal cartilages
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• newborn homozygotes exhibit cricoid cartilage hypoplasia
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• newborn homozygotes exhibit thyroid cartilage hypoplasia
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• newborn homozygotes exhibit malformations in the oropharynx region
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small pharynx
(
J:83662
)
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• at E14.5, homozygotes exhibit a significantly reduced pharynx
• at E9.5, homozygotes display a reduction of pharyngeal endoderm
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small trachea
(
J:83662
)
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• newborn homozygotes display a reduced tracheal size
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hematopoietic system
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• newborn homozygotes lack a thymus (a derivative of the third pharyngeal pouch)
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homeostasis/metabolism
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• at E14.5, homozygotes exhibit severe edema
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digestive/alimentary system
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• newborn homozygotes lack a secondary palate
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• the palatal shelves fail to extend medially to form the secondary palate
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• newborn homozygotes lack an esophagus
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growth/size/body
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• newborn homozygotes lack a secondary palate
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• the palatal shelves fail to extend medially to form the secondary palate
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• newborn homozygotes have external ears that are set abnormally close to the eyes
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small ears
(
J:83662
)
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• newborn homozygotes exhibit small external ears
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• at E8.5, 4 of 50 homozygotes display a reduced body size
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microcephaly
(
J:83662
)
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• newborn homozygotes display microcephaly
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• newborn homozygotes are slightly smaller than wild-type littermates
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immune system
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• newborn homozygotes lack a thymus (a derivative of the third pharyngeal pouch)
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muscle
cellular
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• at E10.5, homozygotes show absence of neural crest cell migration through the peripharyngeal region into the proximity of the heart, resulting in lack of outflow tract septation
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| DiGeorge syndrome | DOID:11198 |
OMIM:188400 |
J:83662 | |
| velocardiofacial syndrome | DOID:12583 |
OMIM:192430 |
J:83662 | |
