Phenotypes associated with this allele

• Allele Symbol: Chrd^tm1Emdr
• Allele Name: targeted mutation 1, EM De Robertis
• Allele ID: MGI:2157350
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chrd^tm1Emdr/Chrd^tm1Emdr	129S6.129-Chrd^tm1Emdr	MGI:3841293
hm2	Chrd^tm1Emdr/Chrd^tm1Emdr	either: B6SJL.129-Chrd^tm1Emdr or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J)	MGI:2676545
hm3	Chrd^tm1Emdr/Chrd^tm1Emdr	involves: 129S1/Sv * 129X1/SvJ	MGI:3819787
hm4	Chrd^tm1Emdr/Chrd^tm1Emdr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:3691482
hm5	Chrd^tm1Emdr/Chrd^tm1Emdr	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:3818961
cx6	Chrd^tm1Emdr/Chrd^tm1Emdr Tbx1^m1Jlk/Tbx1^m1Jlk	129/Sv-Tbx1^m1Jlk Chrd^tm1Emdr	MGI:3841289
cx7	Bmper^tm1Emdr/Bmper^tm1Emdr Chrd^tm1Emdr/Chrd^tm1Emdr	involves: 129 * C57BL/6 * SJL	MGI:3818262
cx8	Chrd^tm1Emdr/Chrd^tm1Emdr Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:2662585
cx9	Chrd^tm1Emdr/Chrd^tm1Emdr Nog^tm1Amc/Nog^tm1Amc	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:2173453
cx10	Chrd^tm1Emdr/Chrd^tm1Emdr Nodal^tm1Rob/Nodal^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ	MGI:4819097
cx11	Chrd^tm1Emdr/Chrd^tm1Emdr Smad3^tm1Xfw/Smad3^+	involves: 129/Sv * 129S1/Sv * 129X1/SvJ	MGI:4819103
cx12	Chrd^tm1Emdr/Chrd^tm1Emdr Smad3^tm1Xfw/Smad3^tm1Xfw	involves: 129/Sv * 129S1/Sv * 129X1/SvJ	MGI:4819104
cx13	Chrd^tm1Emdr/Chrd^tm1Emdr Twsg1^tm1.1Mboc/Twsg1^tm1.1Mboc	involves: 129/Sv * C57BL/6 * FVB/N	MGI:3830685

Genotype
MGI:3841293

hm1

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr
• Genetic Background: 129S6.129-Chrd^tm1Emdr

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Cleft palate and ear and cardiovascular abnormalities in Chrd^tm1Emdr/Chrd^tm1Emdr mice

craniofacial

abnormal pharyngeal arch artery morphology ( J:146769 )

absent mandible ( J:146769 )

• sometimes

short mandible ( J:146769 )

• mandibular truncation with a penetrance of about 20%

cleft palate ( J:146769 )

abnormal ear position ( J:146769 )

• ears are abnormally located at E15.5

abnormal outer ear development ( J:146769 )

• ears fail to form auricle structure

skeleton

absent mandible ( J:146769 )

• sometimes

short mandible ( J:146769 )

• mandibular truncation with a penetrance of about 20%

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:146769 )

persistent truncus arteriosus ( J:146769 )

digestive/alimentary system

cleft palate ( J:146769 )

embryo

abnormal pharyngeal arch artery morphology ( J:146769 )

hearing/vestibular/ear

abnormal ear position ( J:146769 )

• ears are abnormally located at E15.5

abnormal outer ear development ( J:146769 )

• ears fail to form auricle structure

hematopoietic system

athymia ( J:146769 )

immune system

athymia ( J:146769 )

endocrine/exocrine glands

athymia ( J:146769 )

growth/size/body

cleft palate ( J:146769 )

abnormal ear position ( J:146769 )

• ears are abnormally located at E15.5

abnormal outer ear development ( J:146769 )

• ears fail to form auricle structure

Genotype
MGI:2676545

hm2

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr
• Genetic Background: either: B6SJL.129-Chrd^tm1Emdr or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J)

mortality/aging

perinatal lethality, complete penetrance ( J:83662 )

• 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

lethality throughout fetal growth and development, incomplete penetrance ( J:83662 )

• 86% of homozygotes are still alive at E14.5; however, a sharp increase in lethality is noted after E14.5

embryonic lethality between somite formation and embryo turning, complete penetrance ( J:83662 )

• 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

embryo

abnormal neural crest cell migration ( J:83662 )

• 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

abnormal mesoderm development ( J:83662 )

• at E8.5, 4 of 50 homozygotes show early ventralization of the mesoderm, with increased extraembryonic mesodermal cells noted in the allantois

decreased embryo size ( J:83662 )

• at E8.5, 4 of 50 homozygotes display a reduced body size

abnormal embryonic tissue morphology ( J:83662 )

• at E8.5, 4 of 50 homozygotes display a reduced embryonic region, while the remaining 46 appear morphologically normal

absent pharyngeal arches ( J:83662 )

• at E9.0, the second (hyoid) pharyngeal arch is absent

• in addition, pharyngeal arches three to six fail to form

absent mesoderm ( J:83662 )

• at E8.5, 4 of 50 homozygotes display absence of trunk mesoderm

abnormal neural plate morphology ( J:83662 )

• at E8.5, 4 of 50 homozygotes exhibit a significantly hypoplastic and poorly differentiated neural plate

absent notochord ( J:83662 )

• 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

abnormal pharyngeal pouch morphology ( J:83662 )

• at E9.5, the pharyngeal pouches are reduced to a single swelling in the anterior-most region

absent somites ( J:83662 )

• at E8.5, 4 of 50 homozygotes display absence of somites

abnormal extraembryonic tissue morphology ( J:83662 )

enlarged allantois ( J:83662 )

• at E8.5, 4 of 50 homozygotes display an enlarged allantois with an abundance of extraembryonic mesodermal cells

craniofacial

fusion of basioccipital and basisphenoid bone ( J:83662 )

• 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

presphenoid bone hypoplasia ( J:83662 )

• newborn homozygotes display a hypoplastic presphenoid bone

absent temporal bone squamous part ( J:83662 )

• newborn homozygotes lack the squama temporalis

small temporal bone ( J:83662 )

• newborn homozygotes a smaller temporal bone

short zygomatic arch ( J:83662 )

• newborn homozygotes display a shorter zygomatic arch

hyoid bone hypoplasia ( J:83662 )

• newborn homozygotes exhibit hyoid bone hypoplasia

abnormal mandible morphology ( J:83662 )

• newborn homozygotes lack the coronoid, condylar and angular processes

absent mandibular angle ( J:83662 )

• newborn homozygotes lack the angular process

absent mandibular condyloid process ( J:83662 )

• newborn homozygotes lack the condylar process

absent mandibular coronoid process ( J:83662 )

• newborn homozygotes lack the coronoid process

small mandible ( J:83662 )

• newborn homozygotes display an abnormally small jaw

abnormal secondary palate development ( J:83662 )

• newborn homozygotes lack a secondary palate

palatal shelves fail to meet at midline ( J:83662 )

• the palatal shelves fail to extend medially to form the secondary palate

absent pharyngeal arches ( J:83662 )

• at E9.0, the second (hyoid) pharyngeal arch is absent

• in addition, pharyngeal arches three to six fail to form

cleft secondary palate ( J:83662 )

abnormal ear position ( J:83662 )

• newborn homozygotes have external ears that are set abnormally close to the eyes

small ears ( J:83662 )

• newborn homozygotes exhibit small external ears

cardiovascular system

abnormal artery morphology ( J:83662 )

• at E14.5, homozygotes exhibit an enlarged anterior spinal artery

absent pulmonary trunk ( J:83662 )

• in newborns, the pulmonary arteries originate directly from the proximal truncus arteriosus, resulting in the absence of a common pulmonary trunk

abnormal aortic arch morphology ( J:83662 )

• at birth, part of the aortic arch is absent

retroesophageal right subclavian artery ( J:83662 )

• depending of the laterality of the descending aorta, the right or left subclavian arteries adopt an abnormal retrooesophageal position

right aortic arch ( J:83662 )

• 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

abnormal brachiocephalic trunk morphology ( J:83662 )

• absence of the brachiocephalic artery

abnormal common carotid artery morphology ( J:83662 )

• 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

heart right ventricle hypertrophy ( J:83662 )

persistent truncus arteriosus ( J:83662 )

• at E14.5, homozygotes exhibit persistent truncus arteriosus

hemorrhage ( J:83662 )

• at E14.5, homozygotes exhibit severe hemorrhage

increased vasodilation ( J:83662 )

skeleton

fusion of basioccipital and basisphenoid bone ( J:83662 )

• 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

presphenoid bone hypoplasia ( J:83662 )

• newborn homozygotes display a hypoplastic presphenoid bone

absent temporal bone squamous part ( J:83662 )

• newborn homozygotes lack the squama temporalis

small temporal bone ( J:83662 )

• newborn homozygotes a smaller temporal bone

short zygomatic arch ( J:83662 )

• newborn homozygotes display a shorter zygomatic arch

hyoid bone hypoplasia ( J:83662 )

• newborn homozygotes exhibit hyoid bone hypoplasia

abnormal mandible morphology ( J:83662 )

• newborn homozygotes lack the coronoid, condylar and angular processes

absent mandibular angle ( J:83662 )

• newborn homozygotes lack the angular process

absent mandibular condyloid process ( J:83662 )

• newborn homozygotes lack the condylar process

absent mandibular coronoid process ( J:83662 )

• newborn homozygotes lack the coronoid process

small mandible ( J:83662 )

• newborn homozygotes display an abnormally small jaw

abnormal laryngeal cartilage morphology ( J:83662 )

• newborn homozygotes display reduced laryngeal cartilages

cricoid cartilage hypoplasia ( J:83662 )

• newborn homozygotes exhibit cricoid cartilage hypoplasia

thyroid cartilage hypoplasia ( J:83662 )

• newborn homozygotes exhibit thyroid cartilage hypoplasia

abnormal thoracic vertebrae morphology ( J:83662 )

absent arcus anterior ( J:83662 )

• newborn homozygotes lack the anterior arch of the atlas

abnormal vertebral arch development ( J:83662 )

• at E14.5, homozygotes display underdeveloped vertebral neural arches

small vertebral body ( J:83662 )

• 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

hearing/vestibular/ear

abnormal ear position ( J:83662 )

• newborn homozygotes have external ears that are set abnormally close to the eyes

small ears ( J:83662 )

• newborn homozygotes exhibit small external ears

small otic vesicle ( J:83662 )

• at E9.0, otic vesicles are reduced to half their normal diameter

• a conspicuous indentation is noted in the neck region

small otic capsule ( J:83662 )

• newborn homozygotes display a malformed and reduced otic capsule

absent inner ear ( J:83662 )

• newborn homozygotes exhibit hypoplasia/absence of the inner ear

abnormal middle ear morphology ( J:83662 )

absent auditory tube ( J:83662 )

• at E14.5, homozygotes exhibit absence of the Eustachian tube

abnormal tympanic ring morphology ( J:83662 )

• newborn homozygotes display a malformed tympanic ring

decreased tympanic ring size ( J:83662 )

• newborn homozygotes display a reduced tympanic ring

endocrine/exocrine glands

absent parathyroid glands ( J:83662 )

• newborn homozygotes lack parathyroid glands (derivatives of pharyngeal pouches 3 and 4)

athymia ( J:83662 )

• newborn homozygotes lack a thymus (a derivative of the third pharyngeal pouch)

abnormal thyroid gland morphology ( J:83662 )

• newborn homozygotes exhibit a thyroid gland of irregular shape

thyroid gland hypoplasia ( J:83662 )

• newborn homozygotes display thyroid hypoplasia

nervous system

abnormal neural plate morphology ( J:83662 )

• at E8.5, 4 of 50 homozygotes exhibit a significantly hypoplastic and poorly differentiated neural plate

abnormal cranial ganglia morphology ( J:83662 )

• at E9.5, homozygotes display severe cranial sensory ganglia abnormalities, including loss of epibranchial placode-derived ganglia

abnormal vestibulocochlear ganglion morphology ( J:83662 )

• at E9.5, the vestibulocochlear ganglia are deformed and displaced

small geniculate ganglion ( J:83662 )

• at E9.5, the geniculate ganglion is either extremely reduced or entirely absent

absent petrosal ganglion ( J:83662 )

• at E9.5, the petrosal ganglion is either extremely reduced or entirely absent

small petrosal ganglion ( J:83662 )

• at E9.5, the petrosal ganglion is either extremely reduced or entirely absent

abnormal trigeminal ganglion morphology ( J:83662 )

• at E9.5, the trigeminal ganglia are deformed and displaced

absent nodose ganglion ( J:83662 )

• at E9.5, the nodose ganglion is either extremely reduced or entirely absent

small nodose ganglion ( J:83662 )

• at E9.5, the nodose ganglion is either extremely reduced or entirely absent

respiratory system

abnormal laryngeal cartilage morphology ( J:83662 )

• newborn homozygotes display reduced laryngeal cartilages

cricoid cartilage hypoplasia ( J:83662 )

• newborn homozygotes exhibit cricoid cartilage hypoplasia

thyroid cartilage hypoplasia ( J:83662 )

• newborn homozygotes exhibit thyroid cartilage hypoplasia

abnormal oropharynx morphology ( J:83662 )

• newborn homozygotes exhibit malformations in the oropharynx region

small pharynx ( J:83662 )

• at E14.5, homozygotes exhibit a significantly reduced pharynx

• at E9.5, homozygotes display a reduction of pharyngeal endoderm

small trachea ( J:83662 )

• newborn homozygotes display a reduced tracheal size

hematopoietic system

athymia ( J:83662 )

• newborn homozygotes lack a thymus (a derivative of the third pharyngeal pouch)

homeostasis/metabolism

cyanosis ( J:83662 )

• newborn homozygotes appear cyanotic

hydrops fetalis ( J:83662 )

• at E14.5, homozygotes exhibit severe edema

digestive/alimentary system

abnormal secondary palate development ( J:83662 )

• newborn homozygotes lack a secondary palate

palatal shelves fail to meet at midline ( J:83662 )

• the palatal shelves fail to extend medially to form the secondary palate

cleft secondary palate ( J:83662 )

absent esophagus ( J:83662 )

• newborn homozygotes lack an esophagus

growth/size/body

heart right ventricle hypertrophy ( J:83662 )

abnormal secondary palate development ( J:83662 )

• newborn homozygotes lack a secondary palate

palatal shelves fail to meet at midline ( J:83662 )

• the palatal shelves fail to extend medially to form the secondary palate

cleft secondary palate ( J:83662 )

abnormal ear position ( J:83662 )

• newborn homozygotes have external ears that are set abnormally close to the eyes

small ears ( J:83662 )

• newborn homozygotes exhibit small external ears

decreased embryo size ( J:83662 )

• at E8.5, 4 of 50 homozygotes display a reduced body size

microcephaly ( J:83662 )

• newborn homozygotes display microcephaly

decreased body size ( J:83662 )

• newborn homozygotes are slightly smaller than wild-type littermates

immune system

athymia ( J:83662 )

• newborn homozygotes lack a thymus (a derivative of the third pharyngeal pouch)

muscle

heart right ventricle hypertrophy ( J:83662 )

increased vasodilation ( J:83662 )

cellular

abnormal neural crest cell migration ( J:83662 )

• 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

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

Genotype
MGI:3819787

hm3

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

perinatal lethality, incomplete penetrance ( J:123318 )

• about 50% of animals die perinatally

nervous system

nervous system phenotype ( J:123318 )

N • at 2-3 months of age brains show normal gross hippocampal morphology as well as normal dendritic structure

abnormal brain development ( J:123318 )

• axon terminals at hippocampal synapses have more docked vesicles per active zone length than wild-type synapses

enhanced long-term potentiation ( J:123318 )

• LTP induction is enhanced with high frequency stimulation of afferent fibers compared to wild-type controls

abnormal miniature excitatory postsynaptic currents ( J:123318 )

• frequency of mEPSCs in hippocampal slices is significantly increased compared to controls while amplitudes are similar

increased neurotransmitter release ( J:123318 )

enhanced paired-pulse facilitation ( J:123318 )

• in mutant CA1 region hippocampal slices significantly enhanced paired-pulse facilitation (PPF) is observed compared to wild-type slices at interpulse intervals <100 ms

behavior/neurological

decreased exploration in new environment ( J:123318 )

• in Y-maze test mice enter formerly closed (novel) arm of maze less frequently than wild-type controls during recall trial (3 hours after acquisition phase)

abnormal spatial learning ( J:123318 )

• in Morris water maze mice display improved ability to find hidden platform using spatial cues and require less time to escape from water on second day of experiment; after 10 days of training wild-type and mutants show similar performance

abnormal response to novel object ( J:123318 )

• mice display lower sniffing behavior to a novel object placed inside their box during a 15 minute test

hyperactivity ( J:123318 )

• in center of open field mice exhibit hyperactivity and run faster than wild-type controls

Genotype
MGI:3691482

hm4

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

growth/size/body

abnormal outer ear development ( J:60303 )

mortality/aging

perinatal lethality, complete penetrance ( J:60303 )

• homozygotes are stillborn with normal early development and neural induction

embryo

abnormal pharyngeal arch morphology ( J:60303 )

• homozygotes display defects in pharyngeal organization

craniofacial

abnormal pharyngeal arch morphology ( J:60303 )

• homozygotes display defects in pharyngeal organization

abnormal outer ear development ( J:60303 )

cardiovascular system

abnormal cardiovascular development ( J:60303 )

• homozygotes display defects in cardiovascular organization

hearing/vestibular/ear

abnormal ear development ( J:60303 )

• at E12.5, homozygotes exhibit abnormal inner and outer ear development

abnormal outer ear development ( J:60303 )

abnormal inner ear development ( J:60303 )

Genotype
MGI:3818961

hm5

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

mortality/aging

mortality/aging ( J:137629 )

N • Background Sensitivity: mice are viable on this genetic background without the phenotypic abnormalities previously reported for Chrd^tm1Emdr homozygotes

renal/urinary system

renal/urinary system phenotype ( J:130204 )

N • bladder neck-urethra angle is same as in wild-type embryos

reproductive system

reproductive system phenotype ( J:130204 )

N • budding pattern of developing prostate is identical to wild-type embryos several days after initiation of prostatic budding

Genotype
MGI:3841289

cx6

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Tbx1^m1Jlk/Tbx1^m1Jlk
• Genetic Background: 129/Sv-Tbx1^m1Jlk Chrd^tm1Emdr

craniofacial

short mandible ( J:146769 )

• mandibular truncation with a penetrance of about 20%

cleft palate ( J:146769 )

• 100% penetrance

abnormal outer ear morphology ( J:146769 )

• malformed

• 100% penetrance

hematopoietic system

athymia ( J:146769 )

• 100% penetrance

cardiovascular system

persistent truncus arteriosus ( J:146769 )

• 100% penetrance

skeleton

short mandible ( J:146769 )

• mandibular truncation with a penetrance of about 20%

digestive/alimentary system

cleft palate ( J:146769 )

• 100% penetrance

hearing/vestibular/ear

abnormal outer ear morphology ( J:146769 )

• malformed

• 100% penetrance

immune system

athymia ( J:146769 )

• 100% penetrance

endocrine/exocrine glands

athymia ( J:146769 )

• 100% penetrance

growth/size/body

cleft palate ( J:146769 )

• 100% penetrance

abnormal outer ear morphology ( J:146769 )

• malformed

• 100% penetrance

Genotype
MGI:3818262

cx7

• Allelic Composition: Bmper^tm1Emdr/Bmper^tm1Emdr; Chrd^tm1Emdr/Chrd^tm1Emdr
• Genetic Background: involves: 129 * C57BL/6 * SJL

skeleton

abnormal skeleton morphology ( J:141243 )

• mice exhibit the abnormalities observed in both Bmper^tm1Emdr and Chrd^tm1Emdr single homozygotes

decreased rib number ( J:141243 )

• the thirteenth thoracic vertebrae displays a posterior homeotic transformation with loss of the thirteenth rib

thoracic vertebral transformation ( J:141243 )

• the thirteenth thoracic vertebrae displays a posterior homeotic transformation with loss of the thirteenth rib

abnormal vertebral arch morphology ( J:141243 )

• some mice exhibit a weak recovery of neural arches in the lumbar region compared to in Bmper^tm1Emdr homozygotes

Genotype
MGI:2662585

cx8

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:60303 )

• no double homozygotes are recovered among neonates

• only 2 (out of 20 expected) double homozygotes are recovered close to term, both undergoing resorption

embryonic lethality during organogenesis, incomplete penetrance ( J:60303 )

• only 3 (out of 10 expected) double homozygotes are recovered at E12.5

embryonic lethality between somite formation and embryo turning, incomplete penetrance ( J:60303 )

• only 14 (out of 18 expected) double homozygotes are recovered at E8.5

nervous system

abnormal forebrain development ( J:60303 )

• double homozygotes recovered at E12.5 lack extensive areas of the forebrain, anterior to the hindbrain

• at E12.5, telencephalon and diencephalon are reduced to a single thin neural vesicle

• anterior defects are noted at the start of neurulation (E7.5); however, the AVE is initially formed

• in contrast, formation of the midbrain and more posterior brain structures remains unaffected

aprosencephaly ( J:60303 )

• double homozygotes recovered at E12.5 display a more severe phenotype resembling aprosencephaly

holoprosencephaly ( J:60303 )

• double homozygotes recovered close to term exhibit holoprosencephaly

decreased forebrain size ( J:60303 )

• at E8.5, double homozygotes show significant loss of forebrain tissue

abnormal diencephalon morphology ( J:60303 )

• at E12.5, telencephalon and diencephalon are reduced to a single thin neural vesicle

abnormal telencephalon morphology ( J:60303 )

• at E12.5, telencephalon and diencephalon are reduced to a single thin neural vesicle

craniofacial

absent mandible ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit agnathia

absent nasal placodes ( J:60303 )

• double homozygotes recovered at E12.5 lack nasal (olfactory) placodes

abnormal facial morphology ( J:60303 )

• double homozygotes recovered at E12.5 lack extensive facial structures

proboscis ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit a single nasal pit (proboscis)

skeleton

absent mandible ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit agnathia

absent sclerotome ( J:60303 )

• at E12.5, double homozygotes show absence of sclerotome in cervical regions

vision/eye

cyclopia ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit cyclopia

anophthalmia ( J:60303 )

• double homozygotes recovered at E12.5 lack eyes

taste/olfaction

absent nasal placodes ( J:60303 )

• double homozygotes recovered at E12.5 lack nasal (olfactory) placodes

respiratory system

absent nasal placodes ( J:60303 )

• double homozygotes recovered at E12.5 lack nasal (olfactory) placodes

tracheoesophageal fistula ( J:60303 )

• at E8.5, the trachea fails to form, and a common tracheo-esophageal duct connects the pharynx to the lungs and stomach

small pharynx ( J:60303 )

• at E8.5, the anterior pharynx is reduced

cardiovascular system

abnormal direction of heart looping ( J:60303 )

• at early somites stages, double homozygotes exhibit inverted cardiac looping, with the prospective heart ventricle looping to the left

embryo

abnormal mesendoderm development ( J:60303 )

• double homozygotes show defects in dorsal mesendoderm development (notochord, sclerotome, foregut)

abnormal left-right axis patterning ( J:60303 )

• at E8.5, 4 of 7 double homozygotes display heart inversions, indicating randomization of the heart situs

abnormal cephalic neural fold morphology ( J:60303 )

• at early somites stages, double homozygotes display a reduction in anterior neural folds

absent notochord ( J:60303 )

• at E12.5, double homozygotes show absence of a notochord in cervical regions

digestive/alimentary system

tracheoesophageal fistula ( J:60303 )

• at E8.5, the trachea fails to form, and a common tracheo-esophageal duct connects the pharynx to the lungs and stomach

growth/size/body

abnormal facial morphology ( J:60303 )

• double homozygotes recovered at E12.5 lack extensive facial structures

proboscis ( J:60303 )

• holoprosencephalic double homozygotes recovered close to term exhibit a single nasal pit (proboscis)

Genotype
MGI:2173453

cx9

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Nog^tm1Amc/Nog^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

cardiovascular system

abnormal direction of heart looping ( J:137629 )

• at E9.0 mutants show no directional looping of the heart; cardiac looping is abnormal or reversed in >90% of embryos

Genotype
MGI:4819097

cx10

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Nodal^tm1Rob/Nodal⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ

nervous system

holoprosencephaly ( J:161524 )

• in 14 of 19 mice with defects in anterior midline tissues

embryo

abnormal mesendoderm development ( J:161524 )

• expression analysis indicates defects in patterning and function in the anterior most axial mesendoderm

abnormal embryonic tissue morphology ( J:161524 )

• 23% (19 of 83) show defects in anterior midline tissues

• 14 of these 19 show holoprosencephaly in association with anterior body truncation and fused first pharyngeal arches

fused first pharyngeal arch ( J:161524 )

• fused in 14 of 19 mice with defects in anterior midline tissues

abnormal anterior definitive endoderm morphology ( J:161524 )

• expression analysis indicates impairment in ADE specification

abnormal prechordal plate morphology ( J:161524 )

• expression analysis indicates defects in patterning and function

cardiovascular system

abnormal direction of heart looping ( J:161524 )

• cardiac laterality defects are seen in 5 mice

craniofacial

fused first pharyngeal arch ( J:161524 )

• fused in 14 of 19 mice with defects in anterior midline tissues

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly		DOID:4621	OMIM:PS236100	J:161524

Genotype
MGI:4819103

cx11

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Smad3^tm1Xfw/Smad3⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ

embryo

embryo phenotype ( J:161524 )

N • no defects are detected in anterior midline tissues

Genotype
MGI:4819104

cx12

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Smad3^tm1Xfw/Smad3^tm1Xfw
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ

embryo

embryo phenotype ( J:161524 )

N • no defects are detected in anterior midline tissues

Genotype
MGI:3830685

cx13

• Allelic Composition: Chrd^tm1Emdr/Chrd^tm1Emdr; Twsg1^tm1.1Mboc/Twsg1^tm1.1Mboc
• Genetic Background: involves: 129/Sv * C57BL/6 * FVB/N

mortality/aging

perinatal lethality ( J:88784 )

craniofacial

abnormal mandible morphology ( J:88784 )

skeleton

abnormal mandible morphology ( J:88784 )

abnormal vertebral arch morphology ( J:88784 )

nervous system

nervous system phenotype ( J:88784 )

N • no alobar holoprosencephaly at E15.5-E17.5