Phenotypes associated with this allele

• Allele Symbol: Hoxa2^tm1Grid
• Allele Name: targeted mutation 1, Tom Gridley
• Allele ID: MGI:1857530
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hoxa2^tm1Grid/Hoxa2^tm1Grid	involves: 129S/SvEv * 129S1/Sv * C57BL/6 * DBA/2	MGI:3773305
hm2	Hoxa2^tm1Grid/Hoxa2^tm1Grid	involves: 129S1/Sv	MGI:3773318
hm3	Hoxa2^tm1Grid/Hoxa2^tm1Grid	involves: 129S1/Sv * C57BL/6J	MGI:3773317
ht4	Hoxa2^tm1Grid/Hoxa2^+	involves: 129S1/Sv	MGI:3773522
ht5	Hoxa2^tm1(tetO)Mllo/Hoxa2^tm1Grid	involves: 129S1/Sv * C57BL/6J	MGI:3773521
cx6	Hoxa2^tm1Grid/Hoxa2^tm1Grid Satb2^tm1Rug/Satb2^tm1Rug	involves: 129S1/Sv	MGI:3696454

Genotype
MGI:3773305

hm1

• Allelic Composition: Hoxa2^tm1Grid/Hoxa2^tm1Grid
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6 * DBA/2

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

hearing/vestibular/ear

abnormal incus morphology ( J:100238 )

• mice exhibit a duplication of the incus

abnormal malleus morphology ( J:100238 )

• mice exhibit a duplication of the malleus

abnormal otic capsule morphology ( J:100238 )

• the otic capsule contains a rod-like cartilaginous element instead of cartilage and may indicate a duplication in the tympanic bone

craniofacial

abnormal incus morphology ( J:100238 )

• mice exhibit a duplication of the incus

abnormal malleus morphology ( J:100238 )

• mice exhibit a duplication of the malleus

skeleton

abnormal incus morphology ( J:100238 )

• mice exhibit a duplication of the incus

abnormal malleus morphology ( J:100238 )

• mice exhibit a duplication of the malleus

Genotype
MGI:3773318

hm2

• Allelic Composition: Hoxa2^tm1Grid/Hoxa2^tm1Grid
• Genetic Background: involves: 129S1/Sv

mortality/aging

neonatal lethality, complete penetrance ( J:71951 )

• mice die within 24 hours of birth

hearing/vestibular/ear

abnormal stapedial artery morphology ( J:71951 )

• the stapedial artery is displaced rostrally compared to in wild-type mice

abnormal gonial bone morphology ( J:71951 )

abnormal external auditory canal morphology ( J:30826 )

• duplication of the tympanic ring results in a duplication of the external acoustic meatus

absent outer ear ( J:71951 )

• mice lack an external pinna

duplicated tympanic ring ( J:30826 )

• duplication of the tympanic ring results in a duplication of the external acoustic meatus

craniofacial

abnormal basisphenoid bone morphology ( J:71951 )

abnormal temporal bone squamous part morphology ( J:71951 )

abnormal gonial bone morphology ( J:71951 )

abnormal external auditory canal morphology ( J:30826 )

• duplication of the tympanic ring results in a duplication of the external acoustic meatus

absent outer ear ( J:71951 )

• mice lack an external pinna

nervous system

decreased rhombomere 3 size ( J:71951 )

• r3 size is decreased compared to in wild-type mice

abnormal rhombomere boundary morphology ( J:71951 )

• the r1/r2 boundary is absent and the r2/r3 boundary is abnormal

abnormal facial nerve morphology ( J:71951 )

• mice exhibit axons that emanate from more than just r3 contributing to the facial nerve

cardiovascular system

abnormal stapedial artery morphology ( J:71951 )

• the stapedial artery is displaced rostrally compared to in wild-type mice

behavior/neurological

aphagia ( J:71951 )

• mice never feed

skeleton

abnormal basisphenoid bone morphology ( J:71951 )

abnormal temporal bone squamous part morphology ( J:71951 )

abnormal gonial bone morphology ( J:71951 )

embryo

decreased rhombomere 3 size ( J:71951 )

• r3 size is decreased compared to in wild-type mice

abnormal rhombomere boundary morphology ( J:71951 )

• the r1/r2 boundary is absent and the r2/r3 boundary is abnormal

growth/size/body

abnormal external auditory canal morphology ( J:30826 )

• duplication of the tympanic ring results in a duplication of the external acoustic meatus

absent outer ear ( J:71951 )

• mice lack an external pinna

Genotype
MGI:3773317

hm3

• Allelic Composition: Hoxa2^tm1Grid/Hoxa2^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6J

mortality/aging

neonatal lethality, complete penetrance ( J:16389 )

• mice die within 24 hours of birth

craniofacial

abnormal basioccipital bone morphology ( J:16389 )

abnormal Meckel's cartilage morphology ( J:16389 )

• mice exhibit a duplication of Meckel's cartilage

abnormal temporal bone morphology ( J:16389 )

• mice exhibit additional areas undergoing intramembranous ossification that are connected o the squamosal bone

abnormal styloid process morphology ( J:16389 )

• at E13.5 to E15.5, mice lack the cartilaginous primordial of the styloid process

abnormal hyoid bone morphology ( J:16389 )

• at E13.5 to E15.5, mice lack the cartilaginous primordial of the lesser horns of the hyoid bone

abnormal middle ear ossicle morphology ( J:16389 )

• several ectopic cartilages are present in the middle ear unlike in wild-type mice

• mice exhibit increased ossification centers within the middle ear compared to in wild-type mice

absent stapes ( J:16389 )

abnormal secondary palate development ( J:316149 , J:151467 )

• at E12.5-E14.5, palatal shelves exhibit significantly higher Six2 mRNA and protein levels than wild-type palatal shelves (J:316149)

• at E14.5-E15.5, the spatial domain of Six2 protein expression in the palatal mesenchyme is ectopically expanded to include the entire nasal half in addition to the oral half of the palatal shelf (J:316149)

• at E14.5, Six2 immunostaining is faintly visible in medial edge epithelium (MEE) cells located at the apical tips of palatal shelves (J:316149)

• at E13.5, palatal shelves show a higher density of proliferating Ki-67-positive palatal mesenchyme cells as well as a higher density of Six2/Ki-67 double-positive cells than wild-type palatal shelves (J:316149)

• in culture, mouse embryonic palate mesenchymal (MEPM) cells derived from E13.5 embryos show both increased proliferation and elevated Ccnd1 (cyclin D1) mRNA expression relative to wild-type cultures (J:316149)

• BrdU staining showed significantly higher cell proliferation rates in the anterior region of palatal shelves at E12.5, E14.5 and E15.5 and in the medial and posterior regions at E12.5 and E14.5 relative to wild-type shelves (J:151467)

• TUNEL analysis showed no differences in apoptosis at E12.5, E13.5 or E14.5 (J:151467)

abnormal palatal shelf fusion at midline ( J:151467 )

• in vitro, when whole palate explants are cultured in the absence of the tongue, the frequency of fused palates is 44.4% versus 90.0% in wild-type embryos, while the frequency of contacted but not fused palates is 38.5% versus 10% in wild-type embryos

• however, when E14 palate shelves are excised, arranged in pairs with their medial edges in contact and cultured for 72 hr, the frequency of fused palates is ~86% similar to that in wild-type embryos

palatal shelves fail to meet at midline ( J:151467 )

• when whole palate explants are cultured in the absence of the tongue, the frequency of non-contacted palates is 27.8% versus 0% in wild-type embryos

persistence of medial edge epithelium during palatal shelf fusion ( J:316149 )

• palatal shelves fail to establish contact and do not form a midline epithelial seam (MES) at E14.5

cleft secondary palate ( J:16389 )

• mice exhibit a cleft in the secondary palate

failure of palatal shelf elevation ( J:316149 , J:151467 )

• palatal shelves fail to elevate and remain oriented vertically alongside the tongue at E15.5 (J:316149)

• palatal shelves fail to elevate; however, the hyoglossus is properly inserted into the hyoid in embryos with cleft palate suggesting that malpositioning of the tongue may not be the primary cause of cleft palate (J:151467)

abnormal outer ear morphology ( J:16389 )

• the dorsal aspect of the pinna is absent

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:16389 )

• several ectopic cartilages are present in the middle ear unlike in wild-type mice

• mice exhibit increased ossification centers within the middle ear compared to in wild-type mice

absent stapes ( J:16389 )

abnormal outer ear morphology ( J:16389 )

• the dorsal aspect of the pinna is absent

abnormal tubotympanic recess morphology ( J:16389 )

• mice lack a distinct tubotympanic recess although the tissue does begin to form

abnormal tympanic ring morphology ( J:16389 )

• the dorsal and ventral distal tips of the tympanic rings are hyperplastic giving the ring a symmetric shape unlike in wild-type mice

• ossification centers of the tympanic ring do not join at the caudal extremity of the ring

nervous system

nervous system phenotype ( J:16389 )

N • mice exhibit normal hindbrain organization

abnormal facial nerve morphology ( J:16389 )

• the positioning of the facial nerve is altered

abnormal glossopharyngeal nerve morphology ( J:16389 )

• the proximal portion of the glossopharyngeal nerve is absent

abnormal vagus nerve morphology ( J:16389 )

• some mice exhibit a collapse or condensation of the vagus nerve

• the jugular (superior) ganglion of the vagus is decreased in size compared to in wild-type mice

• however, the nodose (inferior) ganglion of the vagus is normal

skeleton

abnormal basioccipital bone morphology ( J:16389 )

abnormal Meckel's cartilage morphology ( J:16389 )

• mice exhibit a duplication of Meckel's cartilage

abnormal temporal bone morphology ( J:16389 )

• mice exhibit additional areas undergoing intramembranous ossification that are connected o the squamosal bone

abnormal styloid process morphology ( J:16389 )

• at E13.5 to E15.5, mice lack the cartilaginous primordial of the styloid process

abnormal hyoid bone morphology ( J:16389 )

• at E13.5 to E15.5, mice lack the cartilaginous primordial of the lesser horns of the hyoid bone

abnormal middle ear ossicle morphology ( J:16389 )

• several ectopic cartilages are present in the middle ear unlike in wild-type mice

• mice exhibit increased ossification centers within the middle ear compared to in wild-type mice

absent stapes ( J:16389 )

digestive/alimentary system

abnormal secondary palate development ( J:316149 , J:151467 )

• at E12.5-E14.5, palatal shelves exhibit significantly higher Six2 mRNA and protein levels than wild-type palatal shelves (J:316149)

• at E14.5-E15.5, the spatial domain of Six2 protein expression in the palatal mesenchyme is ectopically expanded to include the entire nasal half in addition to the oral half of the palatal shelf (J:316149)

• at E14.5, Six2 immunostaining is faintly visible in medial edge epithelium (MEE) cells located at the apical tips of palatal shelves (J:316149)

• at E13.5, palatal shelves show a higher density of proliferating Ki-67-positive palatal mesenchyme cells as well as a higher density of Six2/Ki-67 double-positive cells than wild-type palatal shelves (J:316149)

• in culture, mouse embryonic palate mesenchymal (MEPM) cells derived from E13.5 embryos show both increased proliferation and elevated Ccnd1 (cyclin D1) mRNA expression relative to wild-type cultures (J:316149)

• BrdU staining showed significantly higher cell proliferation rates in the anterior region of palatal shelves at E12.5, E14.5 and E15.5 and in the medial and posterior regions at E12.5 and E14.5 relative to wild-type shelves (J:151467)

• TUNEL analysis showed no differences in apoptosis at E12.5, E13.5 or E14.5 (J:151467)

abnormal palatal shelf fusion at midline ( J:151467 )

• in vitro, when whole palate explants are cultured in the absence of the tongue, the frequency of fused palates is 44.4% versus 90.0% in wild-type embryos, while the frequency of contacted but not fused palates is 38.5% versus 10% in wild-type embryos

• however, when E14 palate shelves are excised, arranged in pairs with their medial edges in contact and cultured for 72 hr, the frequency of fused palates is ~86% similar to that in wild-type embryos

palatal shelves fail to meet at midline ( J:151467 )

• when whole palate explants are cultured in the absence of the tongue, the frequency of non-contacted palates is 27.8% versus 0% in wild-type embryos

persistence of medial edge epithelium during palatal shelf fusion ( J:316149 )

• palatal shelves fail to establish contact and do not form a midline epithelial seam (MES) at E14.5

cleft secondary palate ( J:16389 )

• mice exhibit a cleft in the secondary palate

failure of palatal shelf elevation ( J:316149 , J:151467 )

• palatal shelves fail to elevate and remain oriented vertically alongside the tongue at E15.5 (J:316149)

• palatal shelves fail to elevate; however, the hyoglossus is properly inserted into the hyoid in embryos with cleft palate suggesting that malpositioning of the tongue may not be the primary cause of cleft palate (J:151467)

meteorism ( J:16389 )

• mice do not appear to feed after birth but examination of their stomach and intestinal content reveal air in the stomach and intestine, and small amounts of milk in their stomachs indicating that mice begin to feed but stop likely due to the air in their stomachs

• neonates have a lare amount of air in the stomach and intestines

growth/size/body

abnormal secondary palate development ( J:316149 , J:151467 )

• at E12.5-E14.5, palatal shelves exhibit significantly higher Six2 mRNA and protein levels than wild-type palatal shelves (J:316149)

• at E14.5-E15.5, the spatial domain of Six2 protein expression in the palatal mesenchyme is ectopically expanded to include the entire nasal half in addition to the oral half of the palatal shelf (J:316149)

• at E14.5, Six2 immunostaining is faintly visible in medial edge epithelium (MEE) cells located at the apical tips of palatal shelves (J:316149)

• at E13.5, palatal shelves show a higher density of proliferating Ki-67-positive palatal mesenchyme cells as well as a higher density of Six2/Ki-67 double-positive cells than wild-type palatal shelves (J:316149)

• in culture, mouse embryonic palate mesenchymal (MEPM) cells derived from E13.5 embryos show both increased proliferation and elevated Ccnd1 (cyclin D1) mRNA expression relative to wild-type cultures (J:316149)

• BrdU staining showed significantly higher cell proliferation rates in the anterior region of palatal shelves at E12.5, E14.5 and E15.5 and in the medial and posterior regions at E12.5 and E14.5 relative to wild-type shelves (J:151467)

• TUNEL analysis showed no differences in apoptosis at E12.5, E13.5 or E14.5 (J:151467)

abnormal palatal shelf fusion at midline ( J:151467 )

• in vitro, when whole palate explants are cultured in the absence of the tongue, the frequency of fused palates is 44.4% versus 90.0% in wild-type embryos, while the frequency of contacted but not fused palates is 38.5% versus 10% in wild-type embryos

• however, when E14 palate shelves are excised, arranged in pairs with their medial edges in contact and cultured for 72 hr, the frequency of fused palates is ~86% similar to that in wild-type embryos

palatal shelves fail to meet at midline ( J:151467 )

• when whole palate explants are cultured in the absence of the tongue, the frequency of non-contacted palates is 27.8% versus 0% in wild-type embryos

persistence of medial edge epithelium during palatal shelf fusion ( J:316149 )

• palatal shelves fail to establish contact and do not form a midline epithelial seam (MES) at E14.5

cleft secondary palate ( J:16389 )

• mice exhibit a cleft in the secondary palate

failure of palatal shelf elevation ( J:316149 , J:151467 )

• palatal shelves fail to elevate and remain oriented vertically alongside the tongue at E15.5 (J:316149)

• palatal shelves fail to elevate; however, the hyoglossus is properly inserted into the hyoid in embryos with cleft palate suggesting that malpositioning of the tongue may not be the primary cause of cleft palate (J:151467)

abnormal outer ear morphology ( J:16389 )

• the dorsal aspect of the pinna is absent

meteorism ( J:16389 )

• mice do not appear to feed after birth but examination of their stomach and intestinal content reveal air in the stomach and intestine, and small amounts of milk in their stomachs indicating that mice begin to feed but stop likely due to the air in their stomachs

• neonates have a lare amount of air in the stomach and intestines

Genotype
MGI:3773522

ht4

• Allelic Composition: Hoxa2^tm1Grid/Hoxa2⁺
• Genetic Background: involves: 129S1/Sv

hearing/vestibular/ear

abnormal malleus morphology ( J:71951 )

• while the shape of the malleus is normal it remains attached via a small bridge to the extra cartilage found in the middle ear

craniofacial

abnormal styloid process morphology ( J:71951 )

abnormal retrotympanic process morphology ( J:71951 )

• some mice exhibit slightly larger than normal ossifications at the distal end of the retrotympanic process of the squamous bone

abnormal malleus morphology ( J:71951 )

• while the shape of the malleus is normal it remains attached via a small bridge to the extra cartilage found in the middle ear

nervous system

abnormal rhombomere boundary morphology ( J:71951 )

• the r2/r3 area is slightly reduced in width compared to in wild-type mice

skeleton

abnormal styloid process morphology ( J:71951 )

abnormal retrotympanic process morphology ( J:71951 )

• some mice exhibit slightly larger than normal ossifications at the distal end of the retrotympanic process of the squamous bone

abnormal malleus morphology ( J:71951 )

• while the shape of the malleus is normal it remains attached via a small bridge to the extra cartilage found in the middle ear

embryo

abnormal rhombomere boundary morphology ( J:71951 )

• the r2/r3 area is slightly reduced in width compared to in wild-type mice

Genotype
MGI:3773521

ht5

• Allelic Composition: Hoxa2^{tm1(tetO)Mllo}/Hoxa2^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6J

hearing/vestibular/ear

abnormal stapedial artery morphology ( J:71951 )

• the stapedial artery is displaced rostrally compared to in wild-type mice

absent oval window ( J:71951 )

• the oval window of the otic capsule is absent

abnormal middle ear ossicle morphology ( J:71951 )

• mice exhibit extra cartilage structures in the middle ear

• however, the gonial bone is normal

abnormal malleus morphology ( J:71951 )

• while the shape of the malleus is normal it remains attached via a small bridge to the extra cartilage found in the middle ear

absent stapes ( J:71951 )

abnormal outer ear morphology ( J:71951 )

abnormal tympanic ring morphology ( J:71951 )

• the morphology of the tympanic ring is shorter than in wild-type mice and exhibits a small membranous element close to the distal end

craniofacial

absent oval window ( J:71951 )

• the oval window of the otic capsule is absent

absent styloid process ( J:71951 )

abnormal temporal bone squamous part morphology ( J:71951 )

abnormal hyoid bone lesser horn morphology ( J:71951 )

• the lesser horn of the hyoid bone is smaller or absent compared to in wild-type mice

abnormal middle ear ossicle morphology ( J:71951 )

• mice exhibit extra cartilage structures in the middle ear

• however, the gonial bone is normal

abnormal malleus morphology ( J:71951 )

• while the shape of the malleus is normal it remains attached via a small bridge to the extra cartilage found in the middle ear

absent stapes ( J:71951 )

cleft palate ( J:71951 )

• some mice exhibit a cleft palate

abnormal tongue muscle morphology ( J:71951 )

• tongue and hyoid musculature exhibit abnormal insertion

abnormal outer ear morphology ( J:71951 )

digestive/alimentary system

cleft palate ( J:71951 )

• some mice exhibit a cleft palate

abnormal tongue muscle morphology ( J:71951 )

• tongue and hyoid musculature exhibit abnormal insertion

cardiovascular system

abnormal stapedial artery morphology ( J:71951 )

• the stapedial artery is displaced rostrally compared to in wild-type mice

muscle

abnormal tongue muscle morphology ( J:71951 )

• tongue and hyoid musculature exhibit abnormal insertion

nervous system

nervous system phenotype ( J:71951 )

N • mice exhibit normal hindbrain organization

abnormal facial nerve morphology ( J:71951 )

• only one mouse exhibited abnormal contributions of r4 neurons to the facial nerve

skeleton

absent oval window ( J:71951 )

• the oval window of the otic capsule is absent

absent styloid process ( J:71951 )

abnormal temporal bone squamous part morphology ( J:71951 )

abnormal hyoid bone lesser horn morphology ( J:71951 )

• the lesser horn of the hyoid bone is smaller or absent compared to in wild-type mice

abnormal middle ear ossicle morphology ( J:71951 )

• mice exhibit extra cartilage structures in the middle ear

• however, the gonial bone is normal

abnormal malleus morphology ( J:71951 )

• while the shape of the malleus is normal it remains attached via a small bridge to the extra cartilage found in the middle ear

absent stapes ( J:71951 )

growth/size/body

cleft palate ( J:71951 )

• some mice exhibit a cleft palate

abnormal tongue muscle morphology ( J:71951 )

• tongue and hyoid musculature exhibit abnormal insertion

abnormal outer ear morphology ( J:71951 )

Genotype
MGI:3696454

cx6

• Allelic Composition: Hoxa2^tm1Grid/Hoxa2^tm1Grid; Satb2^tm1Rug/Satb2^tm1Rug
• Genetic Background: involves: 129S1/Sv

skeleton

skeleton phenotype ( J:115876 )

N • the delay in bone formation seen in single Satb2 homozygotes is largely rescued