Phenotypes associated with this allele

• Allele Symbol: Aldh1a2^tm1Ipc
• Allele Name: targeted mutation 1, Pierre Chambon
• Allele ID: MGI:1857891
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Aldh1a2^tm1Ipc/Aldh1a2^tm1Ipc	Not Specified	MGI:2170323
ht2	Aldh1a2^tm1Dll/Aldh1a2^tm1Ipc	involves: CD-1	MGI:2451320
cn3	Aldh1a2^tm1Dll/Aldh1a2^tm1Ipc Tg(Rarb-cre)1Mrc/0	Not Specified	MGI:3575693
cx4	Aldh1a2^tm1Ipc/Aldh1a2^tm1Ipc Del(19Cyp26a1-Cyp26c1)1Hmd/Del(19Cyp26a1-Cyp26c1)1Hmd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3707682

Genotype
MGI:2170323

hm1

• Allelic Composition: Aldh1a2^tm1Ipc/Aldh1a2^tm1Ipc
• Genetic Background: Not Specified

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:54067 )

• embryos die at E10.5

cardiovascular system

abnormal vitelline vasculature morphology ( J:54067 )

• absence of organized vascular network in yolk sac

abnormal myocardium layer morphology ( J:67816 )

• some intracellular gaps; outermost layer has flattened morphology

absent myocardial trabeculae ( J:54067 )

• myocardial trabeculae are absent

thick myocardium ( J:67816 )

• thickened myocardial wall

abnormal heart development ( J:54067 , J:67816 )

• heart at E9.5 was observed as a single dilated tube of endocardial and myocardial layers (J:54067)

• abnormal posterior chamber development; hypoplastic atrial and sinus venosus regions (J:67816)

abnormal fetal atrioventricular canal morphology ( J:67816 )

• does not form

absent atrioventricular cushions ( J:67816 )

abnormal fetal cardiomyocyte morphology ( J:67816 )

• abnormal cardiomyocytes; early differentiation to sarcomeric organization

failure of heart looping ( J:54067 , J:67816 )

• mutant hearts at E9.5 did not undergo looping (J:54067)

• most embryos exhibit no signs of left-right patterning, including the heart outer curvature normally seen at E9.5 (J:67816)

• however, in many cases, a medial groove separating rostral and caudal regions is present and other anterior-posterior landmarks appear properly situated (J:67816)

enlarged heart ( J:54067 )

• dilated

embryo

abnormal vitelline vasculature morphology ( J:54067 )

• absence of organized vascular network in yolk sac

abnormal embryo turning ( J:54067 )

• most embryos do not turn

caudal body truncation ( J:54067 )

• posterior region of the embryo was shortened

decreased embryo size ( J:54067 )

• smaller than littermates after E9.5

abnormal embryonic tissue morphology ( J:54067 )

abnormal pharyngeal arch morphology ( J:54067 )

• absence of most brachial arches; only arch 1 is intact

absent hindlimb buds ( J:54067 )

• posterior limb buds were absent

absent Wolffian ducts ( J:54067 )

• absence of nephritic ducts

abnormal neural tube morphology ( J:54067 )

• irregular folding in the trunk region

incomplete caudal neuropore closure ( J:54067 )

• posterior region of the embryo remained open ventrally

abnormal somite development ( J:54067 )

• small and more densly packed somites

decreased somite size ( J:54067 )

growth/size/body

enlarged heart ( J:54067 )

• dilated

decreased embryo size ( J:54067 )

• smaller than littermates after E9.5

failure of ventral body wall closure ( J:54067 )

• lack of closure of the posterior ventral body wall

nervous system

abnormal neural tube morphology ( J:54067 )

• irregular folding in the trunk region

incomplete caudal neuropore closure ( J:54067 )

• posterior region of the embryo remained open ventrally

craniofacial

small frontonasal prominence ( J:54067 )

• frontonasal region is truncated

abnormal pharyngeal arch morphology ( J:54067 )

• absence of most brachial arches; only arch 1 is intact

muscle

abnormal myocardium layer morphology ( J:67816 )

• some intracellular gaps; outermost layer has flattened morphology

absent myocardial trabeculae ( J:54067 )

• myocardial trabeculae are absent

thick myocardium ( J:67816 )

• thickened myocardial wall

hearing/vestibular/ear

otic vesicle hypoplasia ( J:54067 )

• hypoplastic otocysts with abnormal distance from hindbrain neuroepithelium

limbs/digits/tail

absent hindlimb buds ( J:54067 )

• posterior limb buds were absent

Genotype
MGI:2451320

ht2

• Allelic Composition: Aldh1a2^tm1Dll/Aldh1a2^tm1Ipc
• Genetic Background: involves: CD-1

Outflow tract septation defects and abnormal patterns of aortic arch-derived arteries in Aldh1a2^tm1Dll/Aldh1a2^tm1Dll and Aldh1a2^tm1Dll/Aldh1a2^tm1Ipc mice

mortality/aging

postnatal lethality, complete penetrance ( J:81969 )

• all mutants die before the age of 2 weeks

• however, compound heterozygotes are obtained at the expected Mendelian ratios at E9.5-E12.5 and E13.5-E14.5

cardiovascular system

abnormal artery morphology ( J:81969 )

• at E18.5 or P1, all mutant embryos show abnormal patterns of the aortic arch and/or head and neck great arteries

abnormal pharyngeal arch artery morphology ( J:81969 )

• at E11.5, a single, enlarged vessel caudal to the third arches is observed instead of the distinct fourth and sixth aortic arches observed in wild-type embryos

abnormal third pharyngeal arch artery morphology ( J:81969 )

• at E9.5, no third aortic arches are formed; however, third aortic arches are detectable at E10.5

aberrant origin of the right subclavian artery ( J:81969 )

• in mutants, the right subclavian artery (RSA) originates ectopically from the descending aorta

right aortic arch ( J:81969 )

• at E18.5 or P1, two of 7 mutants show a right-sided aortic arch, one with a double arch

double aortic arch ( J:81969 )

• at E18.5 or P1, one of 7 mutants shows a double aortic arch

abnormal common carotid artery morphology ( J:81969 )

• at E18.5 or P1, most mutants lack, or have shorter, common carotid arteries, their internal and external carotids arising from the aortic arch, the innominate artery, or at midtracheal (instead of upper cervical) level

abnormal left subclavian artery morphology ( J:81969 )

• in mutants, the left subclavian artery (LSA) and left carotid arteries arise from a common trunk or innominate artery

conotruncal ridge hypoplasia ( J:81969 )

• at E14.5, two of 7 mutant embryos exhibit poorly developed conotruncal wedges

persistent truncus arteriosus ( J:81969 )

• at E14.5, five of 7 mutant embryos display a completely unseptated outflow tract (PTA)

ventricular septal defect ( J:81969 )

• at E14.5, all mutant embryos exhibit a ventricular septal defect

embryo

abnormal pharyngeal arch artery morphology ( J:81969 )

• at E11.5, a single, enlarged vessel caudal to the third arches is observed instead of the distinct fourth and sixth aortic arches observed in wild-type embryos

abnormal third pharyngeal arch artery morphology ( J:81969 )

• at E9.5, no third aortic arches are formed; however, third aortic arches are detectable at E10.5

abnormal neural crest cell migration ( J:81969 )

• at E9.5, mutant embryos show abnormal NCC patterning caudally to the second branchial arch; instead of forming separate streams colonizing the third and fourth to sixth arches, NCCs are arranged in a single mass which is poorly connected with the hindbrain

• in contrast, the migratory pathways of more rostral NCC populations (i.e. toward branchial arches 1 and 2) appear normal

absent third pharyngeal arch ( J:81969 )

• at E9.5, mutant embryos show an apparent lack of third branchial arches

pharyngeal arch hypoplasia ( J:81969 )

• at E9.5, mutants exhibit significant hypoplasia of the putative third and fourth to sixth arches, despite the presence of identifiable ectodermal clefts

• in addition, abnormal fusion of the second and third epibranchial placodes is noted at E9.5

abnormal pharyngeal pouch morphology ( J:81969 )

• at E9.5, the second pharyngeal pouch is properly formed; however, no signs of distinct third or fourth pharyngeal pouches are observed

respiratory system

abnormal laryngeal cartilage morphology ( J:81969 )

• at E18.5, mutants display highly abnormal laryngeal cartilages

abnormal cricoid cartilage morphology ( J:81969 )

• at E18.5, the posterior aspect of cricoid cartilage is abnormally segmented into ring-like structures

abnormal thyroid cartilage morphology ( J:81969 )

• at E18.5, an ectopic cartilage connects the hyoid bone and thyroid cartilage

abnormal tracheal cartilage morphology ( J:81969 )

• at E18.5, mutants display highly abnormal, reduced tracheal rings

short trachea ( J:81969 )

• at E18.5, mutants display a short trachea

immune system

thymus hypoplasia ( J:81969 )

• at E18.5, nine of 10 mutants exhibit display aplasia or significant hypoplasia of the thymus

athymia ( J:81969 )

• at E18.5, nine of 10 mutants exhibit display aplasia or significant hypoplasia of the thymus

endocrine/exocrine glands

absent parathyroid glands ( J:81969 )

• at P1, mutants show absence of parathyroid glands, despite a well-formed thyroid gland

thymus hypoplasia ( J:81969 )

• at E18.5, nine of 10 mutants exhibit display aplasia or significant hypoplasia of the thymus

athymia ( J:81969 )

• at E18.5, nine of 10 mutants exhibit display aplasia or significant hypoplasia of the thymus

nervous system

abnormal cranial nerve morphology ( J:81969 )

• at E9.5, mutant embryos display defective cranial nerve developmental in the postotic branchial region

fusion of glossopharyngeal and vagus nerve ( J:81969 )

• at E11.5, mutant embryos display abnormal fusion of cranial nerves IX (glosso-pharyngeal) and X (vagus) in a single bundle and failure to form separate distal ganglia

growth/size/body

decreased body size ( J:81969 )

• at E18.5 or P1, most mutants are slightly smaller but overtly normal relative to wild-type mice

homeostasis/metabolism

cyanosis ( J:81969 )

• at E18.5 or P1, mutant embryos are alive but develop signs of cyanosis and suffocation within a few hours

craniofacial

abnormal pharyngeal arch artery morphology ( J:81969 )

• at E11.5, a single, enlarged vessel caudal to the third arches is observed instead of the distinct fourth and sixth aortic arches observed in wild-type embryos

abnormal third pharyngeal arch artery morphology ( J:81969 )

• at E9.5, no third aortic arches are formed; however, third aortic arches are detectable at E10.5

absent third pharyngeal arch ( J:81969 )

• at E9.5, mutant embryos show an apparent lack of third branchial arches

pharyngeal arch hypoplasia ( J:81969 )

• at E9.5, mutants exhibit significant hypoplasia of the putative third and fourth to sixth arches, despite the presence of identifiable ectodermal clefts

• in addition, abnormal fusion of the second and third epibranchial placodes is noted at E9.5

skeleton

abnormal laryngeal cartilage morphology ( J:81969 )

• at E18.5, mutants display highly abnormal laryngeal cartilages

abnormal cricoid cartilage morphology ( J:81969 )

• at E18.5, the posterior aspect of cricoid cartilage is abnormally segmented into ring-like structures

abnormal thyroid cartilage morphology ( J:81969 )

• at E18.5, an ectopic cartilage connects the hyoid bone and thyroid cartilage

abnormal tracheal cartilage morphology ( J:81969 )

• at E18.5, mutants display highly abnormal, reduced tracheal rings

hematopoietic system

thymus hypoplasia ( J:81969 )

• at E18.5, nine of 10 mutants exhibit display aplasia or significant hypoplasia of the thymus

athymia ( J:81969 )

• at E18.5, nine of 10 mutants exhibit display aplasia or significant hypoplasia of the thymus

cellular

abnormal neural crest cell migration ( J:81969 )

• at E9.5, mutant embryos show abnormal NCC patterning caudally to the second branchial arch; instead of forming separate streams colonizing the third and fourth to sixth arches, NCCs are arranged in a single mass which is poorly connected with the hindbrain

• in contrast, the migratory pathways of more rostral NCC populations (i.e. toward branchial arches 1 and 2) appear normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:81969

Genotype
MGI:3575693

cn3

• Allelic Composition: Aldh1a2^tm1Dll/Aldh1a2^tm1Ipc; Tg(Rarb-cre)1Mrc/0
• Genetic Background: Not Specified

limbs/digits/tail

abnormal digit morphology ( J:97213 )

• abnormal flexure of the forepaw digits, especially of second and third digits

syndactyly ( J:97213 )

• partial syndactyly of the second to forth forelimb digits

muscle

muscle phenotype ( J:97213 )

N • no defect in the size and topology of distal limb muscle groups and their intersections, except for a slight hypoplasia of the extensor radialis muscles

skeleton

skeleton phenotype ( J:97213 )

N • no defect in digit skeleton

nervous system

abnormal motor neuron innervation pattern ( J:97213 )

• an early embryonic loss of a subset of Lim1+ brachial motoneurons, a mispositioning of Islet1+ neurons and inappropriate axonal projections of the nerves innervating extensor limb muscles

Genotype
MGI:3707682

cx4

• Allelic Composition: Aldh1a2^tm1Ipc/Aldh1a2^tm1Ipc; Del(19Cyp26a1-Cyp26c1)1Hmd/Del(19Cyp26a1-Cyp26c1)1Hmd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

nervous system phenotype ( J:119939 )

N • no CNS defects detected or very minor defects found

embryo

abnormal head mesenchyme morphology ( J:119939 )

• head mesenchyme cell numbers are normal in only 50% of mice

growth/size/body

abnormal head mesenchyme morphology ( J:119939 )

• head mesenchyme cell numbers are normal in only 50% of mice