Phenotypes associated with this allele

• Allele Symbol: Rara^tm1Ipc
• Allele Name: targeted mutation 1, Pierre Chambon
• Allele ID: MGI:1857622
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rara^tm1Ipc/Rara^tm1Ipc	involves: 129S2/SvPas	MGI:2665553
hm2	Rara^tm1Ipc/Rara^tm1Ipc	involves: 129S2/SvPas * C57BL/6	MGI:3766011
ht3	Rara^tm1Ipc/Rara^+	involves: 129S2/SvPas	MGI:3053380
cx4	Rara^tm1Ipc/Rara^tm1Ipc Rarb^tm1Ipc/Rarb^+	involves: 129S2/SvPas	MGI:3033851
cx5	Rara^tm2Ipc/Rara^tm2Ipc Rara^tm1Ipc/Rara^+ Rarg^tm1Ipc/Rarg^tm1Ipc	involves: 129S2/SvPas	MGI:3033885
cx6	Rara^tm1Ipc/Rara^tm1Ipc Rarg^tm2Ipc/Rarg^tm2Ipc	involves: 129S2/SvPas	MGI:3758080
cx7	Rara^tm1Ipc/Rara^tm2Ipc Rarg^tm1Ipc/Rarg^+	involves: 129S2/SvPas	MGI:6382285
cx8	Rara^tm1Ipc/Rara^tm1Ipc Rarb^tm1Ipc/Rarb^tm1Ipc	involves: 129S2/SvPas	MGI:2449447
cx9	Rara^tm1Ipc/Rara^tm1Ipc Rarg^tm1Ipc/Rarg^tm1Ipc	involves: 129S2/SvPas	MGI:3033848
cx10	Rara^tm1Ipc/Rara^+ Rarb^tm1Ipc/Rarb^+	involves: 129S2/SvPas	MGI:6382193
cx11	Rara^tm1Ipc/Rara^+ Rarb^tm1Mma/Rarb^tm1Mma	involves: 129S2/SvPas * C57BL/6	MGI:3766017
cx12	Rara^tm1Ipc/Rara^tm1Ipc Rarb^tm1Mma/Rarb^tm1Mma	involves: 129S2/SvPas * C57BL/6	MGI:3766018
cx13	Rara^tm1Ipc/Rara^tm1Ipc Rarb^tm1Mma/Rarb^+	involves: 129S2/SvPas * C57BL/6	MGI:3766015
cx14	Rara^tm1Ipc/Rara^tm1Ipc Rarg^tm4Ipc/Rarg^tm4Ipc	involves: 129/Sv * 129S2/SvPas	MGI:3758079

Genotype
MGI:2665553

hm1

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc
• Genetic Background: involves: 129S2/SvPas

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

Degenerative lesions in testes of 4 to 5 month old Rara^tm1Ipc/Rara^tm1Ipc mice

mortality/aging

premature death ( J:13574 )

• 3% survived to 1 to 2 months of age

neonatal lethality, incomplete penetrance ( J:13574 )

• progressive decline in numbers

• 60% were cannibalized within the first day of birth

skeleton

abnormal skeleton morphology ( J:21009 )

• in 4 of 21 mice

abnormal alisphenoid bone morphology ( J:42773 )

• low penentrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

abnormal hyoid bone morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone

abnormal incus morphology ( J:42773 )

• low penentrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

abnormal cricoid cartilage morphology ( J:42773 )

• 9 of 14 homozygotes show ventral extension of the cricoid cartilage

abnormal thyroid cartilage morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone

abnormal cervical vertebrae morphology ( J:21009 )

• dyssymphysis of cervical neural arches in 3 of 12 mice

abnormal cervical axis morphology ( J:21009 )

• in 3 of 21 mice

cervical vertebral fusion ( J:21009 )

• fusion of neural arches in 1 of 21 mice

cervical vertebral transformation ( J:21009 )

• C2 to C1 anterior transformation in 1 of 21 mice

endocrine/exocrine glands

abnormal testis morphology ( J:13574 )

♂ • degeneration of the germinal epithelium

seminiferous tubule degeneration ( J:13574 )

♂

growth/size/body

postnatal growth retardation ( J:13574 )

• slower growth rate after 1 to weeks of age

limbs/digits/tail

interdigital webbing ( J:13574 )

reproductive system

abnormal testis morphology ( J:13574 )

♂ • degeneration of the germinal epithelium

seminiferous tubule degeneration ( J:13574 )

♂

abnormal spermatogenesis ( J:13574 )

♂

oligozoospermia ( J:13574 )

♂ • reduced presence of spermatozoa in the epididymis

male infertility ( J:13574 )

♂ • males that survived past 2 months of age were incapable of siring offspring

craniofacial

abnormal alisphenoid bone morphology ( J:42773 )

• low penentrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

abnormal hyoid bone morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone

abnormal incus morphology ( J:42773 )

• low penentrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

hearing/vestibular/ear

abnormal incus morphology ( J:42773 )

• low penentrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

respiratory system

abnormal cricoid cartilage morphology ( J:42773 )

• 9 of 14 homozygotes show ventral extension of the cricoid cartilage

abnormal thyroid cartilage morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone

cellular

oligozoospermia ( J:13574 )

♂ • reduced presence of spermatozoa in the epididymis

Genotype
MGI:3766011

hm2

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc
• Genetic Background: involves: 129S2/SvPas * C57BL/6

skeleton

abnormal skeleton morphology ( J:43344 )

• 73% of mutants exhibit malformed skeletons

abnormal temporal bone squamous part morphology ( J:43344 )

• 4 of 15 mutants exhibit a malformed squamosal bone

abnormal thyroid cartilage morphology ( J:43344 )

• 1 of 15 mutants show a thyroid cartilage fused to hyoid bone

abnormal tracheal cartilage morphology ( J:43344 )

• 1 of 15 mutants show tracheal cartilage abnormalities

fusion of atlas and odontoid process ( J:43344 )

• 6 of 15 (40%) mutants show fusion of C1-AA with C2 dens

fusion of vertebral arches ( J:43344 )

• 1 of 15 mutants show fusions of neural arches of C2 and C3

vertebral transformation ( J:43344 )

thoracic vertebral transformation ( J:43344 )

• 3 of 15 (20%) mutants show anterior transformation of T8 to T7

cervical vertebral transformation ( J:43344 )

• 1 of 15 mutants show anterior transformation of C2 to C1

• 3 of 15 mutants show posterior transformation of C7 to T1

lumbar vertebral transformation ( J:43344 )

• 2 of 15 mutants show anterior transformation of L1 to T14

vision/eye

narrow eye opening ( J:43344 )

• display a mild reduction of the palpebral aperture at E14.5

craniofacial

abnormal temporal bone squamous part morphology ( J:43344 )

• 4 of 15 mutants exhibit a malformed squamosal bone

respiratory system

abnormal thyroid cartilage morphology ( J:43344 )

• 1 of 15 mutants show a thyroid cartilage fused to hyoid bone

abnormal tracheal cartilage morphology ( J:43344 )

• 1 of 15 mutants show tracheal cartilage abnormalities

reproductive system

oligozoospermia ( J:98529 )

♂ • young adult male homozygotes show a striking decrease in the number of epididymal spermatozoa relative to wild-type controls

teratozoospermia ( J:98529 )

♂ • most of the remaining mutant epididymal spermatozoa appear defective relative to those of wild-type controls

abnormal spermatid morphology ( J:98529 )

♂ • ~77% of mutant step 8-9 spermatids are randomly oriented with regard to the basal aspect of Sertoli cells in putative stage VIII-IX tubules relative to ~4% of controls

♂ • four (instead of expected three) layers of germ cells are detected in putative stage IX, where late spermatids are retained in the epithelia

♂ • at putative stage VIII, no alignment of mature spermatids at the surface of tubular lumen is observed

♂ • no entrenchment of spermatids within more basal aspects of Sertoli cells is observed in putative stage IV

abnormal male germ cell apoptosis ( J:98529 )

♂ • at 6 weeks of age, TUNEL-positive, peripherally-located elongated spermatids at steps 10-11 of spermiogenesis are noted in mutant testes but never in wild-type testes; the frequency of TUNEL-positive elongated spermatids decreases by 8 and 9 weeks of age

♂ • at 6 weeks of age, TUNEL-positive apoptotic elongated spermatids are detected when deeply embedded in the seminiferous epithelium

♂ • apoptosis of elongating spermatids does not appear to involve pathways mediated by activated caspase-3

♂ • similar to wild-type testes, mutant testes show the highest number of TUNEL-positive germ cells (not including elongated spermatids) at 3-weeks of age; however, mutant testes show a second peak of apoptosis at ~6 weeks, which then drops at 7, 8 and 9 weeks

abnormal spermiogenesis ( J:98529 )

♂ • young adult male homozygotes show specific defects in spermiogenesis, which may correlate with a failure in both spermatid release and spermatid orientation to the basal aspect of Sertoli cells at putative stage VIII

male infertility ( J:98529 )

♂

cellular

oligozoospermia ( J:98529 )

♂ • young adult male homozygotes show a striking decrease in the number of epididymal spermatozoa relative to wild-type controls

teratozoospermia ( J:98529 )

♂ • most of the remaining mutant epididymal spermatozoa appear defective relative to those of wild-type controls

abnormal spermatid morphology ( J:98529 )

♂ • ~77% of mutant step 8-9 spermatids are randomly oriented with regard to the basal aspect of Sertoli cells in putative stage VIII-IX tubules relative to ~4% of controls

♂ • four (instead of expected three) layers of germ cells are detected in putative stage IX, where late spermatids are retained in the epithelia

♂ • at putative stage VIII, no alignment of mature spermatids at the surface of tubular lumen is observed

♂ • no entrenchment of spermatids within more basal aspects of Sertoli cells is observed in putative stage IV

abnormal male germ cell apoptosis ( J:98529 )

♂ • at 6 weeks of age, TUNEL-positive, peripherally-located elongated spermatids at steps 10-11 of spermiogenesis are noted in mutant testes but never in wild-type testes; the frequency of TUNEL-positive elongated spermatids decreases by 8 and 9 weeks of age

♂ • at 6 weeks of age, TUNEL-positive apoptotic elongated spermatids are detected when deeply embedded in the seminiferous epithelium

♂ • apoptosis of elongating spermatids does not appear to involve pathways mediated by activated caspase-3

♂ • similar to wild-type testes, mutant testes show the highest number of TUNEL-positive germ cells (not including elongated spermatids) at 3-weeks of age; however, mutant testes show a second peak of apoptosis at ~6 weeks, which then drops at 7, 8 and 9 weeks

Genotype
MGI:3053380

ht3

• Allelic Composition: Rara^tm1Ipc/Rara⁺
• Genetic Background: involves: 129S2/SvPas

respiratory system

abnormal cricoid cartilage morphology ( J:42773 )

• 3 of 8 heterozygotes show ventral extension of the cricoid cartilage

skeleton

abnormal cricoid cartilage morphology ( J:42773 )

• 3 of 8 heterozygotes show ventral extension of the cricoid cartilage

Genotype
MGI:3033851

cx4

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarb^tm1Ipc/Rarb⁺
• Genetic Background: involves: 129S2/SvPas

cardiovascular system

persistent right dorsal aorta ( J:21034 )

• at E18.5 the right dorsal aortic root which is normally lost persists (2 out of 3)

absent fetal ductus arteriosus ( J:21034 )

• the normal fetal connection between the aorta and the main pulmonary artery (ductus arteriosus) is also absent in mice with persistent truncus arteriosus and is thought to be secondary to this condition

persistent truncus arteriosus ( J:21034 )

• this defect was detected in 2 of 4 mutants at E18.5

perimembraneous ventricular septal defect ( J:21034 )

• in mice with persistent truncus arteriosus defects are also found in the membranous portion of the ventricular septum but not in the muscular portion of the septum at E18.5 (3 out of 4)

renal/urinary system

renal glomerulus hypertrophy ( J:21034 )

• abnormally large glomeruli are found in the cortical region of hypoplastic kidneys

absent nephrogenic zone ( J:21034 )

• the nephrogenic zone of the cortex is absent in hypoplastic kidneys

renal hypoplasia ( J:21034 )

• kidneys are smaller than normal due to bilateral hypoplasia; however, division of the kidney into cortical and medullary regions is still present at E18.5 (3 out of 4)

• kidney hypoplasia is less severe than in double homozygous mice

abnormal renal tubule morphology ( J:21034 )

• abnormally convoluted tubules are found in the cortical region of hypoplastic kidneys

ectopic kidney ( J:21034 )

• hypoplastic kidneys are often ectopic being located in the lower lumbar or sacral regions rather than in the normal upper lumbar site

respiratory system

abnormal respiratory system morphology ( J:21034 )

• multiple defects in tissues derived from the primitive thoracic foregut and associated later mesoderm including the lung parenchyma, tracheobronchial tree, larynx, pharynx, and esophagus were found at E18.5.

• the morphology of the cartilages that make up the larynx and trachea were not examined in these mice

pulmonary hypoplasia ( J:21034 )

• the right and left lungs are hypoplastic (2 out of 4)

• unlike in double homozygous mice the left lung is present but hypoplastic

Genotype
MGI:3033885

cx5

• Allelic Composition: Rara^tm2Ipc/Rara^tm2Ipc; Rara^tm1Ipc/Rara⁺; Rarg^tm1Ipc/Rarg^tm1Ipc
• Genetic Background: involves: 129S2/SvPas

mortality/aging

perinatal lethality ( J:21034 )

cardiovascular system

abnormal cardiovascular system morphology ( J:21034 )

• abnormalities of the heart and abnormalities of the great vessels related to aortic arch patterning defects similar to those seen in offspring of vitamin A deficient rats were seen in these mice at E18.5

persistent right dorsal aorta ( J:21034 )

• the right dorsal aortic root that is normally lost persists (2 out of 5)

abnormal fourth pharyngeal arch artery morphology ( J:21034 )

• the right 4th aortic arch that normally persists is lost (2 out of 5)

double outlet right ventricle ( J:21034 )

• dextroposed ascending aorta - the aorta originates from the right ventricle (2 out of 5)

abnormal interventricular septum membranous part morphology ( J:21034 )

• associated with dextroposition of the aorta, defects are also found in the membranous portion of the ventricular septum but not in the muscular portion of the septum (3 out of 5)

abnormal aortic valve morphology ( J:21034 )

• associated with the defect in aortic morphology the aortic valve has 4 cusps

endocrine/exocrine glands

ectopic parathyroid gland ( J:21034 )

• the parathyroid glands were rostrally displaced and not associated with the thyroid gland

renal/urinary system

renal hypoplasia ( J:21034 )

• the kidneys are smaller than normal due to bilateral hypoplasia however division of the kidney into cortical and medullary regions is still present (2 out of 5)

respiratory system

abnormal respiratory system morphology ( J:21034 )

• multiple defects in the cartilages that make up the skeleton of, the trachea, the extrapulmonary bronchi, and the larynx were found at E18.5

abnormal arytenoid cartilage morphology ( J:21034 )

• the arytenoid cartilage is smaller than normal (11 out of 11)

abnormal cricoid cartilage morphology ( J:21034 )

• the shape of the cricoid cartilage is abnormal (11 out of 11)

cricoid and tracheal cartilage fusion ( J:21034 )

• the cricoid cartilage is abnormally fused to the tracheal rings (11 out of 11)

small thyroid cartilage ( J:21034 )

• the thyroid cartilage is smaller than normal (11 out of 11)

fused bronchial cartilage rings ( J:21034 )

• detailed examination revealed that the cartilages in the caudal portion of the stem bronchi are fused (11 out of 11)

absent tracheal cartilage rings ( J:21034 )

• the tracheal cartilage rings are absent and are replaced by ventral cartilage and cartilaginous nodules (11 out of 11)

skeleton

abnormal arytenoid cartilage morphology ( J:21034 )

• the arytenoid cartilage is smaller than normal (11 out of 11)

abnormal cricoid cartilage morphology ( J:21034 )

• the shape of the cricoid cartilage is abnormal (11 out of 11)

cricoid and tracheal cartilage fusion ( J:21034 )

• the cricoid cartilage is abnormally fused to the tracheal rings (11 out of 11)

small thyroid cartilage ( J:21034 )

• the thyroid cartilage is smaller than normal (11 out of 11)

absent tracheal cartilage rings ( J:21034 )

• the tracheal cartilage rings are absent and are replaced by ventral cartilage and cartilaginous nodules (11 out of 11)

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:21034 )

• the right 4th aortic arch that normally persists is lost (2 out of 5)

embryo

abnormal fourth pharyngeal arch artery morphology ( J:21034 )

• the right 4th aortic arch that normally persists is lost (2 out of 5)

Genotype
MGI:3758080

cx6

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarg^tm2Ipc/Rarg^tm2Ipc
• Genetic Background: involves: 129S2/SvPas

mortality/aging

perinatal lethality, incomplete penetrance ( J:42773 )

• normal numbers are seen at E18.5, however only 3 survive the perinatal period and reach adulthood, indicating that a majority die around birth

renal/urinary system

renal hypoplasia ( J:42773 )

• 2/3 of mutants exhibit kidney hypoplasia

skeleton

abnormal axial skeleton morphology ( J:42773 )

• double mutants exhibit an increase in the frequency and severity of axial skeletal malformations compared to the single mutants

abnormal alisphenoid bone morphology ( J:42773 )

• 80% exhibit a bilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

absent temporal bone zygomatic process ( J:42773 )

• 3 of 4 show bilateral agenesis of the zygomatic process of the squamosal bone

abnormal incus morphology ( J:42773 )

• 80% exhibit a bilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

abnormal cricoid cartilage morphology ( J:42773 )

• ventral extension of the cricoid cartilage; severity is not increased in the double mutant compared to single mutant

abnormal thyroid cartilage morphology ( J:42773 )

• abnormal extensions of both anterior horns of the thyroid cartilage which are fused to the hyoid bone in all mutants

abnormal thoracic vertebrae morphology ( J:42773 )

abnormal cervical vertebrae morphology ( J:42773 )

• 100% penetrance of cervical vertebrae defects

cervical vertebral fusion ( J:42773 )

• 3 of 5 show C2-C3 fusion

abnormal lumbar vertebrae morphology ( J:42773 )

cardiovascular system

right aortic arch ( J:42773 )

• low penetrance (1 of 6 mutants)

absent stapedial artery ( J:42773 )

• low penetrance of agenesis of the stapedial artery (2 of 6 mutants)

craniofacial

abnormal alisphenoid bone morphology ( J:42773 )

• 80% exhibit a bilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

absent temporal bone zygomatic process ( J:42773 )

• 3 of 4 show bilateral agenesis of the zygomatic process of the squamosal bone

abnormal incus morphology ( J:42773 )

• 80% exhibit a bilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

endocrine/exocrine glands

ectopic thymus ( J:42773 )

• low penetrance of the presence of a cervical thymus (1 of 6 mutants)

absent Harderian gland ( J:42773 )

• low penetrance of bilateral Harderian gland agenesis (1 of 6 mutants)

hearing/vestibular/ear

absent stapedial artery ( J:42773 )

• low penetrance of agenesis of the stapedial artery (2 of 6 mutants)

abnormal incus morphology ( J:42773 )

• 80% exhibit a bilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone)

hematopoietic system

ectopic thymus ( J:42773 )

• low penetrance of the presence of a cervical thymus (1 of 6 mutants)

immune system

ectopic thymus ( J:42773 )

• low penetrance of the presence of a cervical thymus (1 of 6 mutants)

respiratory system

abnormal cricoid cartilage morphology ( J:42773 )

• ventral extension of the cricoid cartilage; severity is not increased in the double mutant compared to single mutant

abnormal thyroid cartilage morphology ( J:42773 )

• abnormal extensions of both anterior horns of the thyroid cartilage which are fused to the hyoid bone in all mutants

Genotype
MGI:6382285

cx7

• Allelic Composition: Rara^tm1Ipc/Rara^tm2Ipc; Rarg^tm1Ipc/Rarg⁺
• Genetic Background: involves: 129S2/SvPas

skeleton

abnormal skeleton morphology ( J:21009 )

• in all mice

abnormal neurocranium morphology ( J:21009 )

• a third cartilaginous pillar is fused ventrally to the basisphenoid bone to form a cartilaginous medial wall to the cavum epiptericum unlike in wild-type mice

• shortened braincase and compression by intracranial ectopic cartilaginous and bony nodules in non-exencephalic mice at E18.5

basisphenoid bone foramen ( J:21009 )

• never closes

short frontal bone ( J:21009 )

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

abnormal presphenoid bone morphology ( J:21009 )

abnormal upper incisor morphology ( J:21009 )

• dysplasia in some mice

absent upper incisors ( J:21009 )

• in some mice

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

abnormal nasal septum cartilage morphology ( J:21009 )

• duplication of cartilaginous nasal septum

abnormal sternum morphology ( J:21009 )

• in 3 of 11 mice

rib fusion ( J:21009 )

• in 2 of 11 mice

abnormal cervical vertebrae morphology ( J:21009 )

• fusion of cervical neural arches in all mice

• dyssymphysis of cervical neural arches in 10 of 11 mice

abnormal cervical atlas morphology ( J:21009 )

• in 9 of 11 mice

fusion of atlas and occipital bones ( J:21009 )

• in 2 of 11 mice

abnormal cervical axis morphology ( J:21009 )

• in 5 of 11 mice

cervical vertebral transformation ( J:21009 )

• C2 to C1 in 7 of 11 mice

• C6 to C5 in 8 of 11 mice

• C7 to C6 in 8 of 11 mice

• C7 to T1 of T2 in 3 of 11 mice

hearing/vestibular/ear

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

nervous system

intracerebral hemorrhage ( J:21009 )

• in two exencephalic mice at E18.5

abnormal brain morphology ( J:21009 )

• secondary to increased intracranial pressure caused by shortened braincase and compression by intracranial ectopic cartilaginous and bony nodules in 2 of 5 mice at E18.5

abnormal folding of telencephalic vesicles ( J:21009 )

abnormal lateral ventricle morphology ( J:21009 )

• collapsed

abnormal brain commissure morphology ( J:21009 )

• failure of the rostral interhemispheric commissures (corpus callosum, hippocampal commissure and anterior commissure) in 2 of 5 mice at E18.5

abnormal cerebral hemisphere morphology ( J:21009 )

• small in two exencephalic mice at E18.5

absent cerebellum ( J:21009 )

• in two exencephalic mice at E18.5

absent hindbrain ( J:21009 )

• in two exencephalic mice at E18.5

abnormal meninges morphology ( J:21009 )

• ectopic cartilaginous and bony nodules at E18.5

vision/eye

corneal-lenticular stalk ( J:21009 )

• in 4 of 12 mice

failure of eyelid fusion ( J:21009 )

• in 4 of 12 mice

absent nasolacrimal duct ( J:21009 )

• in all mice

endocrine/exocrine glands

abnormal sublingual duct morphology ( J:21009 )

• bilateral (1 of 5 mice) or unilateral (3 of 5 mice) cystic epithelial formations within the parenchyma

absent sublingual duct ( J:21009 )

• bilateral in 1 of 5 mice, unilateral in 3 of 5 mice

short sublingual duct ( J:21009 )

• bilateral in 1 of 5 mice, unilateral in 3 of 5 mice

absent sublingual gland ( J:21009 )

• bilateral in 1 of 5 mice, unilateral in 3 of 5 mice

abnormal submandibular gland morphology ( J:21009 )

• bilateral cystic dysplasia in 2 of 5 mice

• shortened in all mice

absent Harderian gland ( J:21009 )

• in all mice

cardiovascular system

intracerebral hemorrhage ( J:21009 )

• in two exencephalic mice at E18.5

craniofacial

abnormal neurocranium morphology ( J:21009 )

• a third cartilaginous pillar is fused ventrally to the basisphenoid bone to form a cartilaginous medial wall to the cavum epiptericum unlike in wild-type mice

• shortened braincase and compression by intracranial ectopic cartilaginous and bony nodules in non-exencephalic mice at E18.5

basisphenoid bone foramen ( J:21009 )

• never closes

short frontal bone ( J:21009 )

fusion of atlas and occipital bones ( J:21009 )

• in 2 of 11 mice

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

abnormal presphenoid bone morphology ( J:21009 )

abnormal upper incisor morphology ( J:21009 )

• dysplasia in some mice

absent upper incisors ( J:21009 )

• in some mice

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

midline cleft upper lip ( J:21009 )

• cleft of the median upper lip in some mice

cleft palate ( J:21009 )

abnormal nasal septum cartilage morphology ( J:21009 )

• duplication of cartilaginous nasal septum

shortened head ( J:21009 )

digestive/alimentary system

cleft palate ( J:21009 )

abnormal sublingual duct morphology ( J:21009 )

• bilateral (1 of 5 mice) or unilateral (3 of 5 mice) cystic epithelial formations within the parenchyma

absent sublingual duct ( J:21009 )

• bilateral in 1 of 5 mice, unilateral in 3 of 5 mice

short sublingual duct ( J:21009 )

• bilateral in 1 of 5 mice, unilateral in 3 of 5 mice

absent sublingual gland ( J:21009 )

• bilateral in 1 of 5 mice, unilateral in 3 of 5 mice

abnormal submandibular gland morphology ( J:21009 )

• bilateral cystic dysplasia in 2 of 5 mice

• shortened in all mice

growth/size/body

abnormal upper incisor morphology ( J:21009 )

• dysplasia in some mice

absent upper incisors ( J:21009 )

• in some mice

midline cleft upper lip ( J:21009 )

• cleft of the median upper lip in some mice

cleft palate ( J:21009 )

abnormal nasal septum cartilage morphology ( J:21009 )

• duplication of cartilaginous nasal septum

shortened head ( J:21009 )

respiratory system

abnormal nasal septum cartilage morphology ( J:21009 )

• duplication of cartilaginous nasal septum

Genotype
MGI:2449447

cx8

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarb^tm1Ipc/Rarb^tm1Ipc
• Genetic Background: involves: 129S2/SvPas

mortality/aging

neonatal lethality, complete penetrance ( J:21009 , J:21034 )

• mice delivered by Cesarean survive less than an hour (J:21009)

• these double homozygous mutants exhibit many of the defects characteristic of fetal vitamin A deficiency (J:21034)

reproductive system

abnormal female reproductive system morphology ( J:21034 )

♀ • at E18.5 the uterine tubes, uterus and the cranial vagina that are all derived from the paramesonephric ducts are absent due to the absence of these ducts (6 out of 6)

absent oviduct ( J:21034 )

♀ • absent uterine tubes at E18.5

absent uterus ( J:21034 )

♀ • at E18.5

absent cranial vagina ( J:21034 )

♀ • at E18.5

skeleton

abnormal skeleton morphology ( J:21009 )

• in all mice

abnormal occipital bone morphology ( J:21009 )

• basioccipital exoccipital fusion in 7 of 10 mice

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

abnormal cricoid cartilage morphology ( J:21034 )

• the shape of the cricoid cartilage is unrecognizable (10 out of 10)

cricoid and tracheal cartilage fusion ( J:21034 )

• the cricoid cartilage is abnormally fused to the tracheal rings (10 out of 10)

abnormal thyroid cartilage morphology ( J:21034 )

• the rostral horn of the thyroid cartilage is fused to the greater horn of the hyoid bone (10 out of 10)

abnormal tracheal cartilage morphology ( J:21034 )

• the bifurcation of the tracheal cartilage is premature in these mice (10 out of 10)

abnormal cervical vertebrae morphology ( J:21009 )

• fusion of cervical neural arches in 4 of 10 mice

• dyssymphysis of cervical neural arches in 4 of 10 mice

abnormal cervical atlas morphology ( J:21009 )

• in 8 of 10 mice

fusion of atlas and occipital bones ( J:21009 )

• C2 to C1 in 2 of 10 mice

• C6 to C5 in 8 of 10 mice

• C7 to C6 in 8 of 10 mice

abnormal cervical axis morphology ( J:21009 )

• in 7 of 10 mice

cardiovascular system

persistent right dorsal aorta ( J:21034 )

• at E18.5 the right dorsal aortic root which is normally lost persists (6 out of 7)

abnormal sixth pharyngeal arch artery morphology ( J:21034 )

• the distal portions of the right and left 6th aortic arches are unidentifiable (7 out of 7)

abnormal pulmonary artery morphology ( J:21034 )

• at E18.5, the left pulmonary artery is absent; this defect is associated with the absence of the left lung (6 out of 7)

absent fetal ductus arteriosus ( J:21034 )

• the normal fetal connection between the aorta and the main pulmonary artery (ductus arteriosus) is also absent in mice with persistent truncus arteriosus and is thought to be secondary to this condition

persistent truncus arteriosus ( J:21034 )

• this defect is detected at E18.5 in 100% of double mutants

abnormal interventricular septum membranous part morphology ( J:21034 )

• in mice with persistent truncus arteriosus defects are also found in the membranous portion of the ventricular septum but not in the muscular portion of the septum (7 out of 7)

abnormal aortic valve cusp morphology ( J:21034 )

• associated with the defect in aortic morphology the aortic valve has 4 cusps (7 out of 7)

vision/eye

persistent hyperplastic primary vitreous ( J:21009 )

• fibrous retrolenticular membrane in 14 of 14 mice

digestive/alimentary system

absent anal canal ( J:21034 )

• agenesis of the anal canal with the rectum being separated from the skin by a thick layer of mesenchyme was seen at E18.5 (5 out of 7)

abnormal esophageal epithelium morphology ( J:21034 )

• at E11.5 and E18.5 the epithelium of the esophagotracheal tube and the caudal esophagus is of the columnar ciliated type (7 out of 7)

tracheoesophageal fistula ( J:21034 )

• at E11.5 the tube that will become the esophagus and trachea fails to divide resulting in the absence of the esophagotracheal septum (7 out of 7)

• the epithelium of the esophagotracheal tube is columnar ciliated cells like those normally found in the trachea (7 out of 7)

abnormal stomach epithelium morphology ( J:21034 )

• at E18.5 the epithelium of the cardiac and preventricular portions of the stomach is of the columnar ciliated type (7 out of 7)

embryo

abnormal sixth pharyngeal arch artery morphology ( J:21034 )

• the distal portions of the right and left 6th aortic arches are unidentifiable (7 out of 7)

absent Mullerian ducts ( J:21034 )

• the paramesonephric ducts are absent despite the presence of normal Wolffian ducts resulting in the loss of the uterine tubes, uterus and the cranial vagina which are all derived from the paramesonephric ducts

endocrine/exocrine glands

ectopic parathyroid gland ( J:21034 )

• at E18.5 the parathyroid glands were rostrally displaced and not associated with the thyroid gland

persistent cervical thymus ( J:21034 )

• at E18.5 accessory (cervical) thymus bodies are found in the larynx of these mutants (5 out of 7)

immune system

persistent cervical thymus ( J:21034 )

• at E18.5 accessory (cervical) thymus bodies are found in the larynx of these mutants (5 out of 7)

renal/urinary system

renal glomerulus hypertrophy ( J:21034 )

• abnormally large glomeruli are found in the cortical region of hypoplastic kidneys

abnormal kidney development ( J:52599 )

• at E14, the subcapsular region appears histologically abnormal, as a dense ring of mesenchymal cells lacking ureteric bud ends

• at E12, the distribution of stromal cells in the subcapsular region is abnormal forming a thick peripheral layer devoid of ureteric bud ends

• however, metanephric mesenchymal cell survival and differentiation appear normal

abnormal nephrogenic mesenchyme morphogenesis ( J:52599 )

• nephrogenic mesenchymal cells and ureteric bud ends are localized inside the peripheral layer of putative stromal cells, rather than in their normal position below the renal capsule

absent nephrogenic zone ( J:21034 )

• the nephrogenic zone of the cortex is absent

hydronephrosis ( J:21034 )

• at E18.5 despite the decrease in kidney size hydronephrosis and hydroureter are seen indicating some renal excretory function occurred (7 out of 10)

small kidney ( J:52599 )

• at E14, mutant embryonic kidneys are much smaller than wild-type

renal hypoplasia ( J:21034 )

• at E18.5 the kidneys are smaller than normal due to bilateral hypoplasia; however, division of the kidney into cortical and medullary regions is still present (10 out of 10)

decreased nephron number ( J:52599 )

• nephron formation is reduced

abnormal renal tubule morphology ( J:21034 )

• abnormally convoluted tubules are found in the cortical region of hypoplastic kidneys

ectopic kidney ( J:21034 )

• hypoplastic kidneys are often ectopic being located in the lower lumbar or sacral regions rather than in the normal upper lumbar site

abnormal ureter morphology ( J:21034 )

• all mice exhibiting hydronephrosis and hydroureter had either ectopically terminating ureters that opened into the urethra (5 out of 10) or agenesis of the caudal ureter such that the ureter failed to join any part of the lower genitor-urinary tract (6 out of 10)

ectopic ureter ( J:21034 )

• 5 of 10 mice exhibiting hydronephrosis and hydroureter showed ectopically terminating ureters that opened into the urethra

hydroureter ( J:21034 )

• at E18.5 despite the decrease in kidney size hydronephrosis and hydroureter are seen indicating some renal excretory function occurred (7 out of 10)

impaired branching involved in ureteric bud morphogenesis ( J:52599 )

• at E14, the number of ureteric bud tips is reduced ~4-fold relative to that in wild-type embryos; only 4-5 generations of branches are observed versus 8-9 in wild-type embryos

• impaired ureteric bud branching is likely due to loss of Ret (c-ret) expression in the ureteric bud tips, evident by E12

ectopic ureteric bud ( J:52599 )

• at E14, ureteric bud ends are abnormally located in a recessed position away from the subcapsular region

hearing/vestibular/ear

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

respiratory system

abnormal respiratory system morphology ( J:21034 )

• multiple defects in tissues derived from the primitive thoracic foregut and associated later mesoderm including the lung parenchyma, tracheobronchial tree, larynx, pharynx, and esophagus were found at E18.5

tracheoesophageal fistula ( J:21034 )

• at E11.5 the tube that will become the esophagus and trachea fails to divide resulting in the absence of the esophagotracheal septum (7 out of 7)

• the epithelium of the esophagotracheal tube is columnar ciliated cells like those normally found in the trachea (7 out of 7)

abnormal cricoid cartilage morphology ( J:21034 )

• the shape of the cricoid cartilage is unrecognizable (10 out of 10)

abnormal thyroid cartilage morphology ( J:21034 )

• the rostral horn of the thyroid cartilage is fused to the greater horn of the hyoid bone (10 out of 10)

abnormal left lung morphology ( J:21034 )

• the left lung is absent (6 out of 7) or hypoplastic (1 out of 7)

• examination at E11.5 revealed that the left lung bud is also absent

abnormal left major bronchus morphology ( J:21034 )

• the left stem bronchus is nearly absent at E11.5

abnormal right major bronchus morphology ( J:21034 )

• at E11.5 and E12.5 branching of the right stem bronchus is delayed approximately 24 hours and appears to be the cause the hypoplasia of the right lung

abnormal right lung morphology ( J:21034 )

• the right lung is hypoplastic (7 out of 7)

abnormal right lung accessory lobe morphology ( J:21034 )

• the right lung fails to cross the midline because of hypoplasia in the accessory lobe of the right lung

abnormal tracheal cartilage morphology ( J:21034 )

• the bifurcation of the tracheal cartilage is premature in these mice (10 out of 10)

cricoid and tracheal cartilage fusion ( J:21034 )

• the cricoid cartilage is abnormally fused to the tracheal rings (10 out of 10)

hematopoietic system

persistent cervical thymus ( J:21034 )

• at E18.5 accessory (cervical) thymus bodies are found in the larynx of these mutants (5 out of 7)

craniofacial

craniofacial phenotype ( J:21009 )

N • mice exhibit normal craniofacial skeleton at E18.5

abnormal sixth pharyngeal arch artery morphology ( J:21034 )

• the distal portions of the right and left 6th aortic arches are unidentifiable (7 out of 7)

abnormal occipital bone morphology ( J:21009 )

• basioccipital exoccipital fusion in 7 of 10 mice

fusion of atlas and occipital bones ( J:21009 )

• C2 to C1 in 2 of 10 mice

• C6 to C5 in 8 of 10 mice

• C7 to C6 in 8 of 10 mice

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

Genotype
MGI:3033848

cx9

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarg^tm1Ipc/Rarg^tm1Ipc
• Genetic Background: involves: 129S2/SvPas

mortality/aging

neonatal lethality, complete penetrance ( J:21009 )

• mice delivered by Cesarean survive less than an hour

prenatal lethality, complete penetrance ( J:21034 )

• these double homozygous mutants exhibit many of the defects characteristic of fetal vitamin A deficiency

prenatal lethality, incomplete penetrance ( J:21009 )

• fewer than expected mice are present at E18.5

reproductive system

absent seminal vesicle ( J:21034 )

♂ • these defects, in the vas deferens and seminal gland, are associated with the absence of the caudal-most Wolffian duct

♂ • at E18.5 agenesis of the seminal vesicles is also found in these male mice (2 out of 2)

abnormal uterus morphology ( J:21034 )

♀ • at E18.5 the body of the uterus is absent due to the absence of the caudal paramesonephric ducts (3 out of 3)

absent uterus ( J:21034 )

♀ • the body of the uterus is absent, however the uterine horns were uni- or bilaterally present

absent cranial vagina ( J:21034 )

♀ • at E18.5 the cranial vagina is absent due to the absence of the caudal paramesonephric ducts (3 out of 3)

absent vas deferens ( J:21034 )

♂ • at E 18.5 agenesis or dysplasia of the vas deferens is seen in these mice (2 out of 2)

♂ • agenesis is associated with bilateral agenesis of the kidney

skeleton

abnormal skeleton morphology ( J:21009 , J:21034 )

• in all mice (J:21009)

• the shape of the hyoid bone is abnormal, with the greater horns, body and lesser horns being unrecognizable (6 out of 6) (J:21034)

abnormal neurocranium morphology ( J:21009 )

• underossified when present

basisphenoid bone foramen ( J:21009 )

• never closes

abnormal frontal bone morphology ( J:21009 )

• absent medial portions

abnormal occipital bone morphology ( J:21009 )

• basioccipital exoccipital fusion in 1 of 6 mice

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

absent presphenoid bone ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

absent neurocranium ( J:21009 )

• in mice with exencephaly

abnormal cribriform plate morphology ( J:21009 )

• absent lamina cribiform, replaced with aggregates of cartilaginous and bony nodules or rods

absent upper incisors ( J:21009 )

abnormal maxillary shelf morphology ( J:21009 )

• further apart than in wild-type mice and fused with paramedian swellings most likely nasomedial processes

absent premaxilla ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

abnormal nasal bone morphology ( J:21009 )

• absent medial portions

absent vomer bone ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

abnormal nasal capsule morphology ( J:21009 )

• reduced to laterocaudal rudiments, replaced with aggregates of cartilaginous and bony nodules or rods

abnormal carpal bone morphology ( J:21009 )

• unilateral ectopic distal carpal bone in 1 of 6 mice

• unilateral agenesis of D1 carpal bone in 3 (left) and 2 (right) mice

• bilateral agenesis in the central carpal bone in 5 of 6 mice and unilateral in the remaining mouse

abnormal phalanx morphology ( J:21009 )

• delayed ossification of the metacarpals and/or phalanges bulbous with outline of the synovial joints between phalanges difficult to discern

absent radius ( J:21009 )

• unilateral in 2 of 5 mice

short fibula ( J:21009 )

• with increased diameter of ossification

bowed tibia ( J:21009 )

abnormal metacarpal bone morphology ( J:21009 )

• delayed ossification of the metacarpals and/or phalanges

abnormal arytenoid cartilage morphology ( J:21034 )

• the shape of the arytenoid cartilage is unrecognizable (6 out of 6)

abnormal cricoid cartilage morphology ( J:21034 )

• the shape of the cricoid cartilage is unrecognizable (6 out of 6)

cricoid and tracheal cartilage fusion ( J:21034 )

• the cricoid cartilage is abnormally fused to the tracheal rings (6 out of 6)

abnormal thyroid cartilage morphology ( J:21034 )

• the shape of the thyroid cartilage was unrecognizable (6 out of 6)

abnormal tracheal cartilage morphology ( J:21034 )

• the bifurcation of the tracheal cartilage that gives rise to the bronchi occurs prematurely (6 out of 6)

absent tracheal cartilage rings ( J:21034 )

• the tracheal cartilage rings are absent and are replaced by ventral cartilage and cartilaginous nodules (6 out of 6)

abnormal scapula morphology ( J:21009 )

• malformation or partial agenesis of scapula in 5 of 6 mice

abnormal sternum morphology ( J:21009 )

• in all mice

rib fusion ( J:21009 )

• in 2 of 6 mice

scoliosis ( J:21009 )

• in some mice

abnormal cervical vertebrae morphology ( J:21009 )

• fusion of cervical neural arches in all mice

• dyssymphysis of cervical neural arches in all mice

• ectopic bone in cervical region in 2 of 6 mice

abnormal cervical atlas morphology ( J:21009 )

• in all mice

fusion of atlas and occipital bones ( J:21009 )

• C7 to T1 of T2 in 4 of 6 mice

abnormal cervical axis morphology ( J:21009 )

• in all mice

ectopic cartilage ( J:21034 )

• ectopic cartilage is found at either the base of the heart semilunar cusps, in the diaphragm, or in the peritoneum (2 out of 5)

nervous system

open neural tube ( J:21009 )

• open rhombencephalic neural tube at E10.5 and E11.5

abnormal brain morphology ( J:21009 )

• secondary to increased intracranial pressure caused by shortened braincase and compression by intracranial ectopic cartilaginous and bony nodules in non-exencephalic mice at E18.5

abnormal pituitary gland development ( J:21009 )

• the pituitary gland remains in contact with the pharynx

abnormal brain commissure morphology ( J:21009 )

• failure of the rostral interhemispheric commissures (corpus callosum, hippocampal commissure and anterior commissure)

abnormal telencephalon morphology ( J:21009 )

• underdeveloped telencephalic hemispheres

exencephaly ( J:21009 )

absent cochlear ganglion ( J:21009 )

• at E18.5

abnormal abducens nerve morphology ( J:21009 )

• absence of the motor nucleus

optic nerve coloboma ( J:21009 )

• in all mice

limbs/digits/tail

abnormal autopod morphology ( J:21009 )

• bilateral malformation of the scapholunatum in all mice

abnormal carpal bone morphology ( J:21009 )

• unilateral ectopic distal carpal bone in 1 of 6 mice

• unilateral agenesis of D1 carpal bone in 3 (left) and 2 (right) mice

• bilateral agenesis in the central carpal bone in 5 of 6 mice and unilateral in the remaining mouse

abnormal phalanx morphology ( J:21009 )

• delayed ossification of the metacarpals and/or phalanges bulbous with outline of the synovial joints between phalanges difficult to discern

abnormal pollex morphology ( J:21009 )

• bilateral prepollex agenic or rudimentary in 3 of 6 mice, unilateral in remaining mice

• hypoplastic in 1 of 6 mice

oligodactyly ( J:21009 )

• in some mice

polydactyly ( J:21009 )

• in 1 of 6 mice

abnormal foot pad morphology ( J:21009 )

• twisted hindfoot such that the footplate faces the lateral abdominal wall without syndactyly or other digit malformations

absent radius ( J:21009 )

• unilateral in 2 of 5 mice

short fibula ( J:21009 )

• with increased diameter of ossification

bowed tibia ( J:21009 )

abnormal metacarpal bone morphology ( J:21009 )

• delayed ossification of the metacarpals and/or phalanges

hearing/vestibular/ear

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

absent outer ear ( J:21009 )

• bilateral agenesis of the auricle

small otic vesicle ( J:21009 )

• at E10.5

absent organ of Corti ( J:21009 )

• at E18.5

otic capsule hypoplasia ( J:21009 )

• cartilaginous otic capsule is small and incomplete resulting in the cystic protrusion of the epithelial inner ear within the braincase

digestive/alimentary system

abnormal maxillary shelf morphology ( J:21009 )

• further apart than in wild-type mice and fused with paramedian swellings most likely nasomedial processes

short sublingual duct ( J:21009 )

• in all mice

growth/size/body

absent upper incisors ( J:21009 )

abnormal maxillary shelf morphology ( J:21009 )

• further apart than in wild-type mice and fused with paramedian swellings most likely nasomedial processes

abnormal nasal bone morphology ( J:21009 )

• absent medial portions

abnormal nasal capsule morphology ( J:21009 )

• reduced to laterocaudal rudiments, replaced with aggregates of cartilaginous and bony nodules or rods

abnormal upper lip morphology ( J:21009 )

• absent prolabium (median third of the upper lip)

absent nasal septum ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

short snout ( J:21009 )

midline facial cleft ( J:21009 )

• sagittal median cleft

absent outer ear ( J:21009 )

• bilateral agenesis of the auricle

decreased fetal size ( J:21009 )

• at E18.5

vision/eye

optic nerve coloboma ( J:21009 )

• in all mice

abnormal conjunctiva morphology ( J:21009 )

• absent in 4 of 12 mice

abnormal conjunctival sac morphology ( J:21009 )

• small in all mice

abnormal corneal stroma morphology ( J:21009 )

• in 8 of 12 mice

absent cornea ( J:21009 )

• in 4 of 12 mice

corneal-lenticular stalk ( J:21009 )

• in 4 of 12 mice

absent eye anterior chamber ( J:21009 )

• in all mice

abnormal lens fiber morphology ( J:21009 )

• in 4 of 12 mice

aphakia ( J:21009 )

• in 2 of 12 mice at E12.5

failure of eyelid fusion ( J:21009 )

• in all mice

persistent hyperplastic primary vitreous ( J:21009 )

• in all mice

retina coloboma ( J:21009 )

• in all mice

microphthalmia ( J:21009 )

• small or absent eyes in some mice at E18.5

absent nasolacrimal duct ( J:21009 )

• unilateral in 2 of 3 mice, bilateral in 1 of 3 mice

anophthalmia ( J:21009 )

• small or absent eyes in some mice at E18.5

muscle

ventricle myocardium hypoplasia ( J:21034 )

• the ventricular myocardium is abnormally thin (2 out of 5)

cardiovascular system

abnormal cardiovascular system morphology ( J:21034 )

• abnormalities of the heart and abnormalities of the great vessels related to aortic arch patterning defects similar to those seen in offspring of vitamin A deficient rats were seen in these mice at E18.5

persistent right dorsal aorta ( J:21034 )

• the right dorsal aortic root which is normally lost persists (5 out of 5)

abnormal sixth pharyngeal arch artery morphology ( J:21034 )

• the distal portions of the right and left 6th aortic arches are unidentifiable (3 out of 5)

absent fetal ductus arteriosus ( J:21034 )

• the normal fetal connection between the aorta and the main pulmonary artery (ductus arteriosus) is also absent in mice with persistent truncus arteriosus and is thought to be secondary to this condition

ventricle myocardium hypoplasia ( J:21034 )

• the ventricular myocardium is abnormally thin (2 out of 5)

persistent truncus arteriosus ( J:21034 )

• this defect is detected at E18.5 in 100% of double mutants

abnormal interventricular septum membranous part morphology ( J:21034 )

• in mice with persistent truncus arteriosus defects are also found in the membranous portion of the ventricular septum but not in the muscular portion of the septum (5 out of 5)

abnormal aortic valve morphology ( J:21034 )

• associated with the defect in aortic morphology the aortic valve has 4 cusps

endocrine/exocrine glands

short sublingual duct ( J:21009 )

• in all mice

abnormal pituitary gland development ( J:21009 )

• the pituitary gland remains in contact with the pharynx

ectopic parathyroid gland ( J:21034 )

• at E18.5 the parathyroid glands were rostrally displaced and not associated with the thyroid gland

persistent cervical thymus ( J:21034 )

• at E 18.5 persistent cervical thymus occurs in which the thymus is found in the neck with no trace of thymic tissue in its normal location (5 out of 5)

ectopic thyroid gland ( J:21034 )

• at E18.5 the thyroid glands were located either rostral to their normal location in contact with the hyoid bone or caudal to their normal location within the anterior mediastinum (3 out of 5)

absent seminal vesicle ( J:21034 )

♂ • these defects, in the vas deferens and seminal gland, are associated with the absence of the caudal-most Wolffian duct

♂ • at E18.5 agenesis of the seminal vesicles is also found in these male mice (2 out of 2)

absent Harderian gland ( J:21009 )

• in all mice

immune system

persistent cervical thymus ( J:21034 )

• at E 18.5 persistent cervical thymus occurs in which the thymus is found in the neck with no trace of thymic tissue in its normal location (5 out of 5)

renal/urinary system

abnormal metanephric mesenchyme morphology ( J:21034 )

• at E12.5 the nephric mesenchyme is present but fails to differentiate (N = 1)

absent kidney pelvis ( J:21034 )

• the renal pelvis was always absent in these mice (5 out of 5)

absent kidney ( J:21034 )

• at E18.5 renal agenesis in which no kidney tissue could be found and/or renal aplasia in which a small retroperitoneal mass with randomly dispersed tubules and glomeruli is found caudal to the normal location is seen; these conditions can exist in the same mouse (3 out of 5 for both)

absent ureter ( J:21034 )

• associated with kidney agenesis the ureter on the same side as the agenic kidney is also absent (5 out of 5)

abnormal ureteric bud invasion ( J:21034 )

• when present, the ureteric bud failed to reach the metanephric blastema (N = 2)

absent ureteric bud ( J:21034 )

• at E11.5 the ureteric bud was absent on one or both sides

respiratory system

abnormal respiratory system morphology ( J:21034 )

• at E18.5 multiple defects in the cartilages that make up the skeleton of, the trachea, the extrapulmonary bronchi, and the larynx were found, including a decrease in alcian blue staining suggesting deficient cartilage formation

abnormal nasal bone morphology ( J:21009 )

• absent medial portions

abnormal nasal capsule morphology ( J:21009 )

• reduced to laterocaudal rudiments, replaced with aggregates of cartilaginous and bony nodules or rods

absent nasal septum ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

abnormal arytenoid cartilage morphology ( J:21034 )

• the shape of the arytenoid cartilage is unrecognizable (6 out of 6)

abnormal cricoid cartilage morphology ( J:21034 )

• the shape of the cricoid cartilage is unrecognizable (6 out of 6)

abnormal thyroid cartilage morphology ( J:21034 )

• the shape of the thyroid cartilage was unrecognizable (6 out of 6)

fused bronchial cartilage rings ( J:21034 )

• detailed examination revealed that the cartilages in the caudal portion of the stem bronchi are fused

abnormal tracheal cartilage morphology ( J:21034 )

• the bifurcation of the tracheal cartilage that gives rise to the bronchi occurs prematurely (6 out of 6)

cricoid and tracheal cartilage fusion ( J:21034 )

• the cricoid cartilage is abnormally fused to the tracheal rings (6 out of 6)

absent tracheal cartilage rings ( J:21034 )

• the tracheal cartilage rings are absent and are replaced by ventral cartilage and cartilaginous nodules (6 out of 6)

short trachea ( J:21034 )

• the trachea is shorter than normal

hematopoietic system

persistent cervical thymus ( J:21034 )

• at E 18.5 persistent cervical thymus occurs in which the thymus is found in the neck with no trace of thymic tissue in its normal location (5 out of 5)

embryo

abnormal sixth pharyngeal arch artery morphology ( J:21034 )

• the distal portions of the right and left 6th aortic arches are unidentifiable (3 out of 5)

rudimentary Mullerian ducts ( J:21034 )

• the caudal paramesonephric ducts are absent in females resulting in the loss of the body of the uterus and the cranial vagina, at E18.5 which are derived from these ducts

rudimentary Wolffian ducts ( J:21034 )

• the caudal most Wolffian duct is absent in males at E11.5 (2 out of 2)

open neural tube ( J:21009 )

• open rhombencephalic neural tube at E10.5 and E11.5

umbilical hernia ( J:21009 )

craniofacial

abnormal sixth pharyngeal arch artery morphology ( J:21034 )

• the distal portions of the right and left 6th aortic arches are unidentifiable (3 out of 5)

abnormal neurocranium morphology ( J:21009 )

• underossified when present

basisphenoid bone foramen ( J:21009 )

• never closes

abnormal frontal bone morphology ( J:21009 )

• absent medial portions

abnormal occipital bone morphology ( J:21009 )

• basioccipital exoccipital fusion in 1 of 6 mice

fusion of atlas and occipital bones ( J:21009 )

• C7 to T1 of T2 in 4 of 6 mice

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

absent presphenoid bone ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

absent neurocranium ( J:21009 )

• in mice with exencephaly

abnormal cribriform plate morphology ( J:21009 )

• absent lamina cribiform, replaced with aggregates of cartilaginous and bony nodules or rods

absent upper incisors ( J:21009 )

abnormal maxillary shelf morphology ( J:21009 )

• further apart than in wild-type mice and fused with paramedian swellings most likely nasomedial processes

absent premaxilla ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

abnormal nasal bone morphology ( J:21009 )

• absent medial portions

absent vomer bone ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

abnormal nasal capsule morphology ( J:21009 )

• reduced to laterocaudal rudiments, replaced with aggregates of cartilaginous and bony nodules or rods

abnormal upper lip morphology ( J:21009 )

• absent prolabium (median third of the upper lip)

absent nasal septum ( J:21009 )

• replaced with aggregates of cartilaginous and bony nodules or rods

short snout ( J:21009 )

midline facial cleft ( J:21009 )

• sagittal median cleft

absent outer ear ( J:21009 )

• bilateral agenesis of the auricle

Genotype
MGI:6382193

cx10

• Allelic Composition: Rara^tm1Ipc/Rara⁺; Rarb^tm1Ipc/Rarb⁺
• Genetic Background: involves: 129S2/SvPas

craniofacial

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

endocrine/exocrine glands

abnormal Harderian gland development ( J:21009 )

• bilateral absence of the epithelial rudiments of all intraorbital glands (including lachrymal and Harderian glands) in all mice at E18.5

• however, the stroma is present

hearing/vestibular/ear

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

limbs/digits/tail

short fibula ( J:21009 )

• severe in one mouse, milder in two mice

skeleton

abnormal alisphenoid bone morphology ( J:21009 )

• frequently fused to the incus, which is continuous with a rostrally oriented cartilaginous or osseous rod

abnormal incus morphology ( J:21009 )

• continuous with a rostrally oriented cartilaginous or osseous rod, which is frequently fused with the alisphenoid bone

abnormal incus short process morphology ( J:21009 )

• larger than in wild-type mice

short fibula ( J:21009 )

• severe in one mouse, milder in two mice

vision/eye

absent nasolacrimal duct ( J:21009 )

• in all mice

Genotype
MGI:3766017

cx11

• Allelic Composition: Rara^tm1Ipc/Rara⁺; Rarb^tm1Mma/Rarb^tm1Mma
• Genetic Background: involves: 129S2/SvPas * C57BL/6

skeleton

abnormal skeleton morphology ( J:43344 )

• 9 of 15 (60%) of mutants exhibit skeletal abnormalities

abnormal sternum morphology ( J:43344 )

• 1 of 15 (7%) mutants show sternum malformations

fusion of atlas and odontoid process ( J:43344 )

• 8 of 15 (53%) mutants show fusion of C1-AA with C2 dens

split cervical axis ( J:43344 )

• 2 of 15 (13%) mutants show a bifid C2

cervical vertebral transformation ( J:43344 )

• 1 of 15 (7%) mutants show posterior transformation of C7 to T1

Genotype
MGI:3766018

cx12

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarb^tm1Mma/Rarb^tm1Mma
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:43344 )

• die within at most 12 hours following cesarian delivery at E18.5

embryo

absent Mullerian ducts ( J:43344 )

• 100% penetrance of agenesis of the Mullerian duct

cardiovascular system

abnormal pulmonary artery morphology ( J:43344 )

• aberrant origin of the right pulmonary artery from the ipsilateral arch of the aorta in 1 of 9 mutants and aberrant origin of the right pulmonary artery from ipsilateral common carotid in 1 of 9 mutants

right aortic arch ( J:43344 )

• seen in many mutants

absent stapedial artery ( J:43344 )

• unilateral and bilateral agenesis of the stapedial artery is seen in some fetuses

abnormal inferior vena cava morphology ( J:43344 )

• 2 of 6 mutants show a double inferior vena cava and 1 of 6 mutants exhibit absence of the inferior vena cava

persistent truncus arteriosus ( J:43344 )

• 100% penetrance at E14.5 and E18.5

abnormal conotruncus septation ( J:43344 )

• cono-truncal septum is absent in 100% of mutants

ventricular septal defect ( J:43344 )

• 100% penetrance of high ventricular septal defect

craniofacial

abnormal basioccipital bone morphology ( J:43344 )

• 8 of 8 (100%) mutants show a basioccipital without a hypoglossal nerve foramen

absent hypoglossal canal ( J:43344 )

fusion of atlas and occipital bones ( J:43344 )

• 1 of 8 (13%) mutants show fusion of the basioccipital with C1-AA

abnormal incus morphology ( J:43344 )

• 4 of 6 mutants exhibit a pterygoquadrate element

abnormal gonial bone morphology ( J:43344 )

• 3 of 6 mutants exhibit an abnormal gonial bone

abnormal stapes morphology ( J:43344 )

• 2 of 6 mutants exhibit imperforated stapes

absent stapes obturator foramen ( J:43344 )

• absence of the intercrural foramen of the stapes

digestive/alimentary system

absent anal canal ( J:43344 )

• agenesis of the anal canal; 100% penentrance

tracheoesophageal fistula ( J:43344 )

• 100% of mutants lack the esophagotracheal septum

short sublingual duct ( J:43344 )

• 2 of 6 mutants at E18.5 show shortening of the sublingual duct

endocrine/exocrine glands

short sublingual duct ( J:43344 )

• 2 of 6 mutants at E18.5 show shortening of the sublingual duct

abnormal thymus morphology ( J:43344 )

• mutants exhibit a persistent cervical thymus (a complete thymic lobe in the neck region) and/or the absence of one or both thymic lobes

persistent cervical thymus ( J:43344 )

hearing/vestibular/ear

absent stapedial artery ( J:43344 )

• unilateral and bilateral agenesis of the stapedial artery is seen in some fetuses

abnormal incus morphology ( J:43344 )

• 4 of 6 mutants exhibit a pterygoquadrate element

abnormal gonial bone morphology ( J:43344 )

• 3 of 6 mutants exhibit an abnormal gonial bone

abnormal stapes morphology ( J:43344 )

• 2 of 6 mutants exhibit imperforated stapes

absent stapes obturator foramen ( J:43344 )

• absence of the intercrural foramen of the stapes

hematopoietic system

abnormal thymus morphology ( J:43344 )

• mutants exhibit a persistent cervical thymus (a complete thymic lobe in the neck region) and/or the absence of one or both thymic lobes

persistent cervical thymus ( J:43344 )

immune system

abnormal thymus morphology ( J:43344 )

• mutants exhibit a persistent cervical thymus (a complete thymic lobe in the neck region) and/or the absence of one or both thymic lobes

persistent cervical thymus ( J:43344 )

muscle

diaphragmatic hernia ( J:43344 )

• 3 of 6 mutants at E18.5 exhibit diaphragmatic hernia

nervous system

abnormal hypoglossal nerve morphology ( J:43344 )

• lack the foramen of the hypoglossal nerve

renal/urinary system

hydronephrosis ( J:43344 )

• 5 of 6 mutants exhibit hydronephrosis, probably secondary to ectopic ureteral openings or involution of the caudal ureter

renal hypoplasia ( J:43344 )

• 100% penetrance

abnormal ureter morphology ( J:43344 )

• 3 of 6 mutants exhibit agenesis of the caudal ureter at E18.5

ectopic ureter ( J:43344 )

• all mutants at E14.5 and 4 of 6 mutants at E18.5 exhibit ectopic ureteral openings

reproductive system

absent oviduct ( J:43344 )

♀ • agenesis of the oviduct

absent uterus ( J:43344 )

♀ • agenesis of the uterus

absent cranial vagina ( J:43344 )

♀ • agenesis of the cranial vagina

respiratory system

tracheoesophageal fistula ( J:43344 )

• 100% of mutants lack the esophagotracheal septum

abnormal arytenoid cartilage morphology ( J:43344 )

• 100% of mutants have a misshapen arytenoid cartilage

abnormal cricoid cartilage morphology ( J:43344 )

• 100% of mutants have a misshapen cricoid cartilage

abnormal thyroid cartilage morphology ( J:43344 )

• 7 of 8 (88%) mutants show a thyroid cartilage fused to hyoid bone

• 100% of mutants have a misshapen thyroid cartilage

pulmonary hypoplasia ( J:43344 )

• lung agenesis or hypoplasia

abnormal tracheal cartilage morphology ( J:43344 )

• 100% of mutants have tracheal cartilage malformations

skeleton

abnormal skeleton morphology ( J:43344 )

• 100% of mutants show skeletal malformations

abnormal basioccipital bone morphology ( J:43344 )

• 8 of 8 (100%) mutants show a basioccipital without a hypoglossal nerve foramen

absent hypoglossal canal ( J:43344 )

abnormal incus morphology ( J:43344 )

• 4 of 6 mutants exhibit a pterygoquadrate element

abnormal gonial bone morphology ( J:43344 )

• 3 of 6 mutants exhibit an abnormal gonial bone

abnormal stapes morphology ( J:43344 )

• 2 of 6 mutants exhibit imperforated stapes

absent stapes obturator foramen ( J:43344 )

• absence of the intercrural foramen of the stapes

abnormal xiphoid process morphology ( J:43344 )

• 100% of mutants show a xiphoid process malformation; xiphoid process shows delayed ossification

abnormal vertebrae morphology ( J:43344 )

fusion of atlas and occipital bones ( J:43344 )

• 1 of 8 (13%) mutants show fusion of the basioccipital with C1-AA

fusion of atlas and odontoid process ( J:43344 )

• 5 of 8 (63%) mutants show fusion of C1-AA with C2 dens

split cervical atlas ( J:43344 )

• 1 of 8 (13%) mutants show a bifid C1

split cervical axis ( J:43344 )

• 2 of 8 (25%) mutants show a bifid C2

abnormal vertebral arch morphology ( J:43344 )

• 7 of 8 (88%) mutants show dyssymphysis of C1 neural arch

fusion of vertebral arches ( J:43344 )

• 4 of 8 (50%) mutants show fusions of neural arches of C2 and C3

vertebral transformation ( J:43344 )

cervical vertebral transformation ( J:43344 )

• 3 of 8 (38%) mutants show anterior transformation of C2 to C1

• 6 of 8 (76%) mutants show anterior transformation of C6 to C5

lumbar vertebral transformation ( J:43344 )

• 5 of 8 (63%) mutants show anterior transformation of L1 to T14

abnormal cartilage morphology ( J:43344 )

abnormal arytenoid cartilage morphology ( J:43344 )

• 100% of mutants have a misshapen arytenoid cartilage

abnormal cricoid cartilage morphology ( J:43344 )

• 100% of mutants have a misshapen cricoid cartilage

abnormal thyroid cartilage morphology ( J:43344 )

• 7 of 8 (88%) mutants show a thyroid cartilage fused to hyoid bone

• 100% of mutants have a misshapen thyroid cartilage

abnormal tracheal cartilage morphology ( J:43344 )

• 100% of mutants have tracheal cartilage malformations

vision/eye

persistent hyperplastic primary vitreous ( J:43344 )

• complete penetrance of persistent hyperplastic primary vitreous

Genotype
MGI:3766015

cx13

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarb^tm1Mma/Rarb⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

skeleton

abnormal skeleton morphology ( J:43344 )

• 100% of mutants show skeletal malformations

abnormal temporal bone squamous part morphology ( J:43344 )

• 11 of 14 mutants exhibit malformed squamosal bone

abnormal incus morphology ( J:43344 )

• 7 of 14 mutants exhibit a pterygoquadrate element

abnormal thyroid cartilage morphology ( J:43344 )

• 1 of 15 (7%) mutants shows thyroid cartilage fused to hyoid bone

abnormal tracheal cartilage morphology ( J:43344 )

• 3 of 15 (20%) mutants show tracheal cartilage malformations

abnormal vertebrae morphology ( J:43344 )

fusion of atlas and odontoid process ( J:43344 )

• 8 of 15 (53%) mutants show fusion of C1-AA with C2 dens

split cervical atlas ( J:43344 )

• 3 of 15 (20%) mutants show a bifid C1

split cervical axis ( J:43344 )

• 5 of 15 (33%) mutants show a bifid C2

fusion of vertebral arches ( J:43344 )

• 2 of 15 (13%) mutants show fusions of neural arches of C2 and C3

vertebral transformation ( J:43344 )

thoracic vertebral transformation ( J:43344 )

• 6 of 15 (40%) mutants show anterior transformation of L1 to T14

cervical vertebral transformation ( J:43344 )

• 3 of 15 (20%) mutants show anterior transformation of C2 to C1

hearing/vestibular/ear

abnormal incus morphology ( J:43344 )

• 7 of 14 mutants exhibit a pterygoquadrate element

craniofacial

abnormal temporal bone squamous part morphology ( J:43344 )

• 11 of 14 mutants exhibit malformed squamosal bone

abnormal incus morphology ( J:43344 )

• 7 of 14 mutants exhibit a pterygoquadrate element

respiratory system

abnormal thyroid cartilage morphology ( J:43344 )

• 1 of 15 (7%) mutants shows thyroid cartilage fused to hyoid bone

abnormal tracheal cartilage morphology ( J:43344 )

• 3 of 15 (20%) mutants show tracheal cartilage malformations

Genotype
MGI:3758079

cx14

• Allelic Composition: Rara^tm1Ipc/Rara^tm1Ipc; Rarg^tm4Ipc/Rarg^tm4Ipc
• Genetic Background: involves: 129/Sv * 129S2/SvPas

mortality/aging

perinatal lethality ( J:42773 )

renal/urinary system

renal hypoplasia ( J:42773 )

• 5 of 6 show bilateral kidney hypoplasia

absent kidney ( J:42773 )

• 1 of 6 shows kidney agenesis

skeleton

abnormal axial skeleton morphology ( J:42773 )

• double mutants exhibit an increase in the frequency and severity of axial skeletal malformations compared to the single mutants

abnormal alisphenoid bone morphology ( J:42773 )

• penetrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone) is similar to that seen in single homozygous Rara mutants (3 of 16 mutants)

absent temporal bone zygomatic process ( J:42773 )

• 6 of 10 show bilateral agenesis of the zygomatic process of the squamosal bone

abnormal hyoid bone morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone (1 of 6)

abnormal incus morphology ( J:42773 )

• penetrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone) is similar to that seen in single homozygous Rara mutants (3 of 16 mutants)

abnormal cricoid cartilage morphology ( J:42773 )

• the ventral extension of the cricoid cartilage is markedly longer in the double mutant than in either single mutant

abnormal thyroid cartilage morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone (1 of 6)

abnormal thoracic vertebrae morphology ( J:42773 )

abnormal cervical vertebrae morphology ( J:42773 )

• 100% penetrance of cervical vertebrae defects

cervical vertebral fusion ( J:42773 )

• 7 of 9 show C2-C3 fusion

• 5 of 9 show C1-C2 fusion

abnormal lumbar vertebrae morphology ( J:42773 )

cardiovascular system

right aortic arch ( J:42773 )

• low penetrance (1 of 6 mutants)

persistent truncus arteriosus ( J:42773 )

• low penetrance (1 of 6 mutants)

craniofacial

abnormal alisphenoid bone morphology ( J:42773 )

• penetrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone) is similar to that seen in single homozygous Rara mutants (3 of 16 mutants)

absent temporal bone zygomatic process ( J:42773 )

• 6 of 10 show bilateral agenesis of the zygomatic process of the squamosal bone

abnormal hyoid bone morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone (1 of 6)

abnormal incus morphology ( J:42773 )

• penetrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone) is similar to that seen in single homozygous Rara mutants (3 of 16 mutants)

hearing/vestibular/ear

abnormal incus morphology ( J:42773 )

• penetrance of a unilateral pterygoquadrate element (a cartilaginous or osseous extension fusing the incus to the alisphenoid bone) is similar to that seen in single homozygous Rara mutants (3 of 16 mutants)

respiratory system

abnormal cricoid cartilage morphology ( J:42773 )

• the ventral extension of the cricoid cartilage is markedly longer in the double mutant than in either single mutant

abnormal thyroid cartilage morphology ( J:42773 )

• low penetrance of fusion between the greater horns of thyroid cartilage and the hyoid bone (1 of 6)