Phenotypes associated with this allele

• Allele Symbol: Ece1^tm1Reh
• Allele Name: targeted mutation 1, Robert E Hammer
• Allele ID: MGI:2158947
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ece1^tm1Reh/Ece1^tm1Reh	involves: 129S6/SvEvTac	MGI:3036224
hm2	Ece1^tm1Reh/Ece1^tm1Reh	involves: 129S6/SvEvTac * C57BL/6	MGI:3036180
hm3	Ece1^tm1Reh/Ece1^tm1Reh	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3036222
hm4	Ece1^tm1Reh/Ece1^tm1Reh	involves: 129S6/SvEvTac * C57BL/6J	MGI:3815024
cx5	Ece1^tm1Reh/Ece1^tm1Reh Ece2^tm1Ywa/Ece2^tm1Ywa	involves: 129S6/SvEvTac * C57BL/6J	MGI:3037339
cx6	Ece1^tm1Reh/Ece1^+ Ece2^tm1Ywa/Ece2^tm1Ywa	involves: 129S6/SvEvTac * C57BL/6J	MGI:3037348

Genotype
MGI:3036224

hm1

• Allelic Composition: Ece1^tm1Reh/Ece1^tm1Reh
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:46640 )

• most embryos die prior to E13.5

• Background Sensitivity: 100% embryonic lethal in a pure 129S/SvEv background

Genotype
MGI:3036180

hm2

• Allelic Composition: Ece1^tm1Reh/Ece1^tm1Reh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:46640 )

• those mutants that do survive to term die within 30 minutes of birth

embryonic lethality during organogenesis, incomplete penetrance ( J:46640 )

• Background Sensitivity: 75% embryonic lethal in a C57BL/6-129/SvEv hybrid background

• most embryos die before E13.5

pigmentation

abnormal Harderian gland pigmentation ( J:46640 )

• neural crest-derived Harderian gland melanocytes are absent

abnormal epidermal melanocyte morphology ( J:46640 )

• there are no detectable melanocytes in the dorsal skin of term mutants

abnormal choroid melanocyte morphology ( J:46640 )

• the neural crest derived melanocytes of the choroid are absent

cardiovascular system

interrupted aortic arch ( J:46640 )

• interruption of the aortic arch is observed at birth (18 out of 31)

absent right subclavian artery ( J:46640 )

• the right subclavian artery is absent (7 out of 31)

atrioventricular cushion hypoplasia ( J:46640 )

• the endocardial cushions are poorly developed

double outlet right ventricle ( J:46640 )

• the aorta arises from the right ventricle resulting in double outlet right ventricle (3 out of 10)

overriding aortic valve ( J:46640 )

• the aorta overrides the crest of the ventricular septum in 5 out 10 pups

ventricular septal defect ( J:46640 )

• ventricular septal defects are found in 100% (10 out of 10) of mutant embryos at birth

enlarged heart ( J:46640 )

• the atria are congested and dilated

pericardial effusion ( J:46640 )

• along with dilation of the peripheral vasculature this is consistent with cardiac failure

abnormal vasodilation ( J:46640 )

• peripheral vascular dilation is seen in premorbid embryos

craniofacial

abnormal styloid process morphology ( J:46640 )

• the styloid process is severely deformed

absent Meckel's cartilage ( J:46640 )

• at birth Meckel's cartilage is absent

alisphenoid bone hypoplasia ( J:46640 )

• the alisphenoid cone is hypoplastic and deformed

abnormal temporal bone squamous part morphology ( J:46640 )

• the squamosal bone is hypoplastic and deformed

temporal bone squamous part hypoplasia ( J:46640 )

small mandible ( J:46640 )

• at birth the mandible is markedly reduced in size

• the teeth are normal however the lower incisors are embedded in loose mesenchyme rather than the mandible

palatine bone hypoplasia ( J:46640 )

• the palatine bone is hypoplastic and deformed

absent middle ear ossicles ( J:46640 )

absent incus ( J:46640 )

absent malleus ( J:46640 )

absent stapes ( J:46640 )

• the cartilaginous rudiment of the stapes is absent in 11 out of 14 embryos

absent tongue ( J:46640 )

• at birth most of the tongue is absent

absent external auditory canal ( J:46640 )

• the external auditory meatus is absent

endocrine/exocrine glands

absent sublingual duct ( J:46640 )

• at birth sublingual ducts are absent

abnormal submandibular duct morphology ( J:46640 )

• at birth many of the submandibular ducts are missing

parathyroid hypoplasia ( J:46640 )

• the parathyroid glands are hypoplastic

persistent cervical thymus ( J:46640 )

• the thymus does not fully descend into the thoracic cavity

thyroid gland hypoplasia ( J:46640 )

abnormal Harderian gland pigmentation ( J:46640 )

• neural crest-derived Harderian gland melanocytes are absent

hearing/vestibular/ear

absent middle ear ossicles ( J:46640 )

absent incus ( J:46640 )

absent malleus ( J:46640 )

absent stapes ( J:46640 )

• the cartilaginous rudiment of the stapes is absent in 11 out of 14 embryos

absent external auditory canal ( J:46640 )

• the external auditory meatus is absent

absent tympanic ring ( J:46640 )

• the tympanic ring is absent

homeostasis/metabolism

pericardial effusion ( J:46640 )

• along with dilation of the peripheral vasculature this is consistent with cardiac failure

hydrops fetalis ( J:46640 )

• generalized edema is seen in premorbid embryos

immune system

persistent cervical thymus ( J:46640 )

• the thymus does not fully descend into the thoracic cavity

muscle

abnormal vasodilation ( J:46640 )

• peripheral vascular dilation is seen in premorbid embryos

skeleton

abnormal skeleton morphology ( J:46640 )

• the ventral neck is sunken

• at birth fusion of the hyoid bone, thyroid cartilage and the basiphenoid bone, is seen resulting in a narrower airway

abnormal styloid process morphology ( J:46640 )

• the styloid process is severely deformed

absent Meckel's cartilage ( J:46640 )

• at birth Meckel's cartilage is absent

alisphenoid bone hypoplasia ( J:46640 )

• the alisphenoid cone is hypoplastic and deformed

abnormal temporal bone squamous part morphology ( J:46640 )

• the squamosal bone is hypoplastic and deformed

temporal bone squamous part hypoplasia ( J:46640 )

small mandible ( J:46640 )

• at birth the mandible is markedly reduced in size

• the teeth are normal however the lower incisors are embedded in loose mesenchyme rather than the mandible

palatine bone hypoplasia ( J:46640 )

• the palatine bone is hypoplastic and deformed

absent middle ear ossicles ( J:46640 )

absent incus ( J:46640 )

absent malleus ( J:46640 )

absent stapes ( J:46640 )

• the cartilaginous rudiment of the stapes is absent in 11 out of 14 embryos

vision/eye

abnormal choroid melanocyte morphology ( J:46640 )

• the neural crest derived melanocytes of the choroid are absent

nervous system

absent enteric neurons ( J:46640 )

• enteric neurons are missing from the rectum of mutants at birth

• at E12.0 enteric neurons are seen only in the proximal gut and are absent beyond the ileocecal junction

digestive/alimentary system

palatine bone hypoplasia ( J:46640 )

• the palatine bone is hypoplastic and deformed

absent tongue ( J:46640 )

• at birth most of the tongue is absent

absent sublingual duct ( J:46640 )

• at birth sublingual ducts are absent

abnormal submandibular duct morphology ( J:46640 )

• at birth many of the submandibular ducts are missing

hematopoietic system

persistent cervical thymus ( J:46640 )

• the thymus does not fully descend into the thoracic cavity

growth/size/body

enlarged heart ( J:46640 )

• the atria are congested and dilated

palatine bone hypoplasia ( J:46640 )

• the palatine bone is hypoplastic and deformed

absent tongue ( J:46640 )

• at birth most of the tongue is absent

absent external auditory canal ( J:46640 )

• the external auditory meatus is absent

integument

abnormal epidermal melanocyte morphology ( J:46640 )

• there are no detectable melanocytes in the dorsal skin of term mutants

Genotype
MGI:3036222

hm3

• Allelic Composition: Ece1^tm1Reh/Ece1^tm1Reh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

cardiovascular system

abnormal artery morphology ( J:48566 )

• the branchial arch artery patterning abnormalities result in various types of great vessel malformations

persistent ductus caroticus ( J:48566 )

• at E12.5 in approximately 50% of embryos both right and left ductus caroticus remain

persistent right dorsal aorta ( J:48566 )

• at E12.0 - 12.5 and E13.0 - 13.5 the right dorsal aorta remains (6 out of 13 and 6 out of 7)

• at E13.0 the connection of the right dorsal aorta to the abdominal dorsal aorta persists

• in 2 of these embryos right sided dorsal aorta is observed where left arch arteries 4 and 6 and right arch artery 4 regress, while right arch artery 6 and the right dorsal aorta persist and form the major outflow tract from the heart

abnormal fourth pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

• at E12.0 - 12.5 and E13.0 - 13.5 right arch artery 4 shows signs of regression including decreased diameter and expression of a transgenic lacZ marker of arterial smooth muscle (11 out of 13 and 5 out of 7, respectively)

• at E12.0 - 12.5 and E13.0 - 13.5 regression of left arch artery 4 is also seen but not as frequently (7 out of 13 and 4 out of 7, respectively)

• between E11.5 and E13.5 the fourth arch arteries are diminished

abnormal sixth pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

persistent right 6th pharyngeal arch artery ( J:48566 )

• at E12.0 - 12.5 in 6 out of 13 embryos right arch artery 6 abnormally persists

• at E13.0 in embryos where the right arch artery 4 regressed the right arch artery 6 persisted

abnormal third pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

• at E12.0 - 12.5 right arch artery 3 is markedly enlarged in 6 out of 13 embryos

• at E12.5 arch arteries 3 become the dominant vessels bilaterally, accepting blood from the outflow tract

• at E12.5 the overall growth of arch arteries 3 toward the cranial direction is delayed and the external carotid fails to branch off of arch arteries 3

aberrant origin of the right subclavian artery ( J:48566 )

• the right subclavian artery is missing or has a cervical origin in term embryos as a result of abnormal regression of right arch artery 4

• in term embryos with abnormal regression of right arch artery 4 and normal regression of the right ductus caroticus, the right dorsal aorta persists and the right subclavian artery is missing or originates from the dorsal aorta

double aortic arch ( J:48566 )

• double aortic arch is found in term embryos when both the right and left arch arteries 4 abnormally regress or when left arch artery 6 abnormally regresses

abnormal ascending aorta morphology ( J:48566 )

• at E13.0 some embryos have extra branches from the ascending aorta

persistent truncus arteriosus ( J:48566 )

double outlet right ventricle ( J:48566 )

overriding aortic valve ( J:48566 )

• other outflow tract abnormalities such as overriding aorta, double outlet right ventricle, and persistent truncus arteriosus are observed

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

• at E12.0 - 12.5 and E13.0 - 13.5 right arch artery 4 shows signs of regression including decreased diameter and expression of a transgenic lacZ marker of arterial smooth muscle (11 out of 13 and 5 out of 7, respectively)

• at E12.0 - 12.5 and E13.0 - 13.5 regression of left arch artery 4 is also seen but not as frequently (7 out of 13 and 4 out of 7, respectively)

• between E11.5 and E13.5 the fourth arch arteries are diminished

abnormal sixth pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

persistent right 6th pharyngeal arch artery ( J:48566 )

• at E12.0 - 12.5 in 6 out of 13 embryos right arch artery 6 abnormally persists

• at E13.0 in embryos where the right arch artery 4 regressed the right arch artery 6 persisted

abnormal third pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

• at E12.0 - 12.5 right arch artery 3 is markedly enlarged in 6 out of 13 embryos

• at E12.5 arch arteries 3 become the dominant vessels bilaterally, accepting blood from the outflow tract

• at E12.5 the overall growth of arch arteries 3 toward the cranial direction is delayed and the external carotid fails to branch off of arch arteries 3

embryo

abnormal fourth pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

• at E12.0 - 12.5 and E13.0 - 13.5 right arch artery 4 shows signs of regression including decreased diameter and expression of a transgenic lacZ marker of arterial smooth muscle (11 out of 13 and 5 out of 7, respectively)

• at E12.0 - 12.5 and E13.0 - 13.5 regression of left arch artery 4 is also seen but not as frequently (7 out of 13 and 4 out of 7, respectively)

• between E11.5 and E13.5 the fourth arch arteries are diminished

abnormal sixth pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

persistent right 6th pharyngeal arch artery ( J:48566 )

• at E12.0 - 12.5 in 6 out of 13 embryos right arch artery 6 abnormally persists

• at E13.0 in embryos where the right arch artery 4 regressed the right arch artery 6 persisted

abnormal third pharyngeal arch artery morphology ( J:48566 )

• in E11.5 embryos 75% (6/8) show enlargement of right arch artery 3 and relative narrowing of arch arteries 4 and 6

• this occurred more frequently on the right side (6 out of 8 than on the left 3 out of 8)

• at E12.0 - 12.5 right arch artery 3 is markedly enlarged in 6 out of 13 embryos

• at E12.5 arch arteries 3 become the dominant vessels bilaterally, accepting blood from the outflow tract

• at E12.5 the overall growth of arch arteries 3 toward the cranial direction is delayed and the external carotid fails to branch off of arch arteries 3

Genotype
MGI:3815024

hm4

• Allelic Composition: Ece1^tm1Reh/Ece1^tm1Reh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

Cardiac defects in Ece1^tm1Reh/Ece1^tm1Reh and Ece1^tm1Reh/Ece1^tm1Reh Ece2^tm1Ywa/Ece2^tm1Ywa embryos

cardiovascular system

abnormal heart and great artery attachment ( J:62261 )

• malalignment of great vessels and ventricles; the alignment between aortic and pulmonary vessel outflows remains in a spiral position as in wild-type, but the aortic valve and outflow shift rostrally and to the right so that the two valves appear in the same plane

persistent truncus arteriosus ( J:62261 )

• seen in one of ten mutants

double outlet right ventricle ( J:62261 )

• seen in a few mutants

overriding aortic valve ( J:62261 )

• seen in many mutants

perimembraneous ventricular septal defect ( J:62261 )

• most mutants show perimembranous ventricular septal defect

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
double outlet right ventricle		DOID:6406	OMIM:217095	J:62261

Genotype
MGI:3037339

cx5

• Allelic Composition: Ece1^tm1Reh/Ece1^tm1Reh; Ece2^tm1Ywa/Ece2^tm1Ywa
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

Cardiac defects in Ece1^tm1Reh/Ece1^tm1Reh and Ece1^tm1Reh/Ece1^tm1Reh Ece2^tm1Ywa/Ece2^tm1Ywa embryos

mortality/aging

prenatal lethality, incomplete penetrance ( J:62261 )

• the number of alive double homozygous mutant embryos decreased after E12.5

• the ratio of double homozygous embryos that survived until birth tended to be less than that of single Ece1 homozygous mutant embryos, but this difference did not reach statistical significance

cardiovascular system

abnormal cardiovascular system morphology ( J:62261 )

• double homozygous mutant embryos developed cardiac abnormalities that were broader and more severe than those of single Ece1 homozygous mutant embryos

persistent truncus arteriosus ( J:62261 )

• cardiac abnormalities included total or localized defects of the aorticopulmonary septum, which resulted in persistent truncus arteriosus or aorticopulmonary window

failure of atrioventricular cushion closure ( J:62261 )

• in severe cases, the endocardial cushion was hypoplastic and did not form atrioventricular valves at all

double outlet right ventricle ( J:62261 )

• seen in more than half of the mutants

perimembraneous ventricular septal defect ( J:62261 )

abnormal heart valve morphology ( J:62261 )

• double homozygous mutant embryos displayed defects in spiraling of the conotruncal ridges and aorticopulmonary septum; these resulted in a parallel position of the aortic and pulmonary outflow tracts without crossing over each other, with the two valves observed side by side on the same transverse plane

abnormal atrioventricular valve morphology ( J:62261 )

• atrioventricular valves opened toward a ventricular septal defect but not to the left ventricle

abnormal atrioventricular valve development ( J:62261 )

• double homozygous mutant embryos frequently displayed abnormal atrioventricular valve formation, a phenotype never observed in single Ece1 homozygous mutant embryos

craniofacial

mandible hypoplasia ( J:62261 )

• near-term or E20.0 double homozygous mutant embryos had a hypoplastic mandible

abnormal outer ear morphology ( J:62261 )

• near-term or E20.0 double homozygous mutant embryos had hypoplastic pinnae

embryo

embryo phenotype ( J:62261 )

N • double E16.0-E20.0 homozygous mutant embryos displayed defects in multiple neural crest-derived tissues, which were identical to those observed in single Ece1 homozygous mutant embryos

N • at E12.5, the endothelin-1/endothelin-2 levels in whole double homozygous mutant embryos did not differ significantly from those of single Ece1 homozygous mutant embryos

hearing/vestibular/ear

abnormal outer ear morphology ( J:62261 )

• near-term or E20.0 double homozygous mutant embryos had hypoplastic pinnae

skeleton

abnormal skeleton morphology ( J:62261 )

• near-term or E20.0 double homozygous mutant embryos displayed a shrunken anterior neck

mandible hypoplasia ( J:62261 )

• near-term or E20.0 double homozygous mutant embryos had a hypoplastic mandible

growth/size/body

abnormal outer ear morphology ( J:62261 )

• near-term or E20.0 double homozygous mutant embryos had hypoplastic pinnae

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
double outlet right ventricle		DOID:6406	OMIM:217095	J:62261

Genotype
MGI:3037348

cx6

• Allelic Composition: Ece1^tm1Reh/Ece1⁺; Ece2^tm1Ywa/Ece2^tm1Ywa
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:62261 )

• mice heterozygous for Ece1^tm1Reh and homozygous for Ece2^tm1Ywa were healthy and fertile, and appeared indistinguishable from Ece1^tm1Reh heterozygous mutant mice