Phenotypes Associated with This Genotype

Genotype
MGI:2175066

hm2

• Allelic Composition: Hoxa1^tm1Ipc/Hoxa1^tm1Ipc
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:23837 )

• homozygous mutant embryos die at birth from anoxia

homeostasis/metabolism

cyanosis ( J:23837 )

• homozygotes fail to turn pink within 15 min after Cesarean section

anoxia ( J:23837 )

• homozygotes die from anoxia

respiratory system

respiratory failure ( J:23837 )

• homozygotes fail to commence breathing; their lungs never inflate prior to death

• homozygotes lack the roots of the glossopharyngeal (IX) and vagus (X) nerves and are therefore unable to transmit respiratory stimuli to the hindbrain

muscle

muscle spasm ( J:23837 )

• at 15-45 min after Cesarean delivery, homozygotes show spasmodic muscular contractions, with arching of the back and neck

nervous system

delayed neural tube closure ( J:23837 )

• at E9.5, 3 of 6 homozygotes exhibit a variable delay in neural tube closure at the hinbrain level (r2 to r8)

• however, closure eventually occurs such that no significant differences in this region hindbrain are observed at E10.5 or later

abnormal rhombomere morphology ( J:23837 )

• at E15.5 and E17.5, homozygotes show multiple defects in the region corresponding to the level of r4 to r7

abnormal hindbrain morphology ( J:23837 )

• at E15.5 and E17.5, homozygotes show variable malformations of that part of the rhombencephalon derived from r4 to r7

absent facial nuclei ( J:23837 )

• at E15.5 and E17.5, the motor nucleus of the facial nerve (derived from r4 and r5) is absent

absent cochlear ganglion ( J:23837 , J:71547 )

• at E15.5, homozygotes lack cochlear ganglion cells (J:71547)

• 30% of 5RA-treated homozygotes display rescued cochlear ganglion cells (J:71547)

abnormal superior vagus ganglion morphology ( J:23837 )

• at E15.5, the superior ganglion (jugular) of the vagus (X) nerve is malformed or absent

• in contrast, the inferior ganglion (nodose) of the vagus (X) nerve is apparently normal

small vestibular ganglion ( J:23837 )

abnormal cranial nerve morphology ( J:23837 )

• at E15.5 and E17.5, the nuclei of cranial nerves VI and VIII-XI are most likely absent, as is the nucleus of cranial nerve VII

• notably, the hypoglossal (XII) nerve nucleus, partly originating in r8) is normal

absent facial nerve ( J:23837 )

• at E15.5 and E17.5, the mutant facial nerve and nerve root are absent

abnormal glossopharyngeal nerve morphology ( J:23837 )

• at E15.5 and E17.5, the root of the glossopharyngeal (IX) nerve is absent

abnormal vagus nerve morphology ( J:23837 )

• at E15.5 and E17.5, the root of the vagus (X) nerve is absent

absent vestibulocochlear nerve ( J:23837 )

• at E15.5 and E17.5, the root of the acoustic (VIII) nerve is absent

hearing/vestibular/ear

small otic vesicle ( J:71547 )

• at E12.0, homozygotes display small otocysts displaced laterally from the neural tube

• 35% of 5RA-treated homozygotes exhibit improved otocyst morphology

abnormal inner ear morphology ( J:23837 , J:71547 )

• at E15.5 and E17.5, homozygotes display variable inner ear abnormalities (J:23837)

• at E18.5, homozygotes show subtle symmetrical alterations of the bones surrounding the inner ear (J:23837)

• a single maternal administration of a sub-teratogenic dose (5 mg/kg) of retinoic acid (5RA) between E8.0 + 2 hrs (otic placode stage, 5RA-8) and E8.75 (early otic cup stage, 5RA-8.85) rescues both vestibular and cochlear structural defects in mutant mice (J:71547)

abnormal cochlea morphology ( J:71547 )

• at E18.5, the mutant cochlea is either absent (48%) or present as a poorly developed, inflated cystic capsule (52%)

abnormal cochlear sensory epithelium morphology ( J:71547 )

• at E15.5, the cochlear neurosensory region is absent

absent cochlea ( J:23837 , J:71547 )

• at E18.5, the mutant cochlea is absent (J:23837)

• 31% of 5RA-8-treated homozygotes display rescue of cochlear structures; the extent of rescue is often asymmetrical between the two ears (J:71547)

• only 25% of cochleae are absent in 5RA-8- or 5RA-8.75-treated mutant mice relative to 48% in untreated mutant mice (J:71547)

absent common crus ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the common crus

absent posterior semicircular canal ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the posterior semicircular canal

abnormal crista ampullaris morphology ( J:71547 )

• at E15.5, the number and spatial distribution of the cristae is variable, depending on the extent of vestibular defects

• in 5RA-8-treated homozygotes, the degree of rescue of semicircular canals, utricle, and saccule correlate with the recovery of normal numebr/distribution of cristae and macule

absent superior semicircular canal ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the anterior semicircular canal

• in contrast, the lateral semicircular canal is present

absent semicircular canals ( J:23837 )

abnormal inner ear vestibule morphology ( J:71547 )

• at E18.5, vestibular structures are either severely underdeveloped or highly dysmorphic

• 5RA-8-treated homozygotes display rescue of vestibular structures

abnormal membranous labyrinth morphology ( J:23837 , J:71547 )

• at E15.5 and E17.5, homozygotes exhibit a dilated membranous labyrinth of rudimentary morphology (J:23837)

• at E16.0, 62% of homozygotes show a severely abnormal membranous labyrinth; the remaining 38% show a less severe but highly dysmorphic phenotype with identifiable semicircular canals of abnormal planes lumen and size and inner ear structures that resemble an inflated sac (J:71547)

• 27% of 5RA-8.25-8.75-treated homozygotes exhibit a morphologically improved membranous labyrinth, with a similar degree of rescue to that of the cartilaginous capsules: the endolyphatic duct, semicircular canals, utricle, saccule, cochlear duct are present while recovery of cochlear turning is evident in all but one (J:71547)

• in 5RA-8-treated homozygotes, the degree of rescue of semicircular canals, utricle, and saccule correlate with the recovery of normal numebr/distribution of cristae and macule (J:71547)

absent scala media ( J:23837 )

abnormal utricular macula morphology ( J:71547 )

• at E15.5, the number and spatial distribution of the maculae is variable, depending on the extent of vestibular defects

• in 5RA-8-treated homozygotes, the degree of rescue of semicircular canals, utricle, and saccule correlate with the recovery of normal numebr/distribution of cristae and macule

absent utricle ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the utricle

abnormal vestibular saccular macula morphology ( J:71547 )

• at E15.5, the number and spatial distribution of the maculae is variable, depending on the extent of vestibular defects

• in 5RA-8-treated homozygotes, the degree of rescue of semicircular canals, utricle, and saccule correlate with the recovery of normal numebr/distribution of cristae and macule

absent vestibular saccule ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the saccule

absent endolymphatic duct ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the endolymphatic duct

absent endolymphatic sac ( J:71547 )

• at E16.0, 62% of homozygotes show absence of the endolymphatic sac

abnormal otic capsule morphology ( J:23837 )

• at E15.5 and E17.5, the mutant periotic capsule is incomplete ventromedially; as a result, the membranous labyrinth protrudes into adjacent soft tissues

abnormal tympanic ring morphology ( J:23837 )

• at E18.5, the mutant tympanic ring is of normal size but abnormal position

craniofacial

abnormal basioccipital bone morphology ( J:23837 , J:71547 )

• at E18.5, the mutant basioccipital bone lacks a concave lateral border (J:23837)

• at E18.5, the anterior edge of the basioccipital is abnormal; this defect is often not rescued by RA treatment (J:71547)

abnormal interparietal bone morphology ( J:23837 )

• at E18.5, the mutant interparietal bone exhibits a more acute outline at its lateral extremities

abnormal exoccipital bone morphology ( J:23837 )

• at E18.5, mutant exoccipital bones are compressed along the rostrocaudal axis

skeleton

abnormal basioccipital bone morphology ( J:23837 , J:71547 )

• at E18.5, the mutant basioccipital bone lacks a concave lateral border (J:23837)

• at E18.5, the anterior edge of the basioccipital is abnormal; this defect is often not rescued by RA treatment (J:71547)

abnormal interparietal bone morphology ( J:23837 )

• at E18.5, the mutant interparietal bone exhibits a more acute outline at its lateral extremities

abnormal exoccipital bone morphology ( J:23837 )

• at E18.5, mutant exoccipital bones are compressed along the rostrocaudal axis

embryo

delayed neural tube closure ( J:23837 )

• at E9.5, 3 of 6 homozygotes exhibit a variable delay in neural tube closure at the hinbrain level (r2 to r8)

• however, closure eventually occurs such that no significant differences in this region hindbrain are observed at E10.5 or later

abnormal rhombomere morphology ( J:23837 )

• at E15.5 and E17.5, homozygotes show multiple defects in the region corresponding to the level of r4 to r7