Phenotypes associated with this allele

• Allele Symbol: Hoxa1^tm3.1Mrc
• Allele Name: targeted mutation 3.1, Mario R Capecchi
• Allele ID: MGI:2151686
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hoxa1^tm3.1Mrc/Hoxa1^tm3.1Mrc	involves: 129S1/Sv * 129X1/SvJ	MGI:3773293
ht2	Hoxa1^tm3.1Mrc/Hoxa1^tm4(Hoxb1)Mrc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3703013
cx3	Hoxa1^tm3.1Mrc/Hoxa1^tm3.1Mrc Hoxb1^tm3Mrc/Hoxb1^tm3Mrc	involves: 129S1/Sv * 129X1/SvJ	MGI:3773291
cx4	Hoxa1^tm3.1Mrc/Hoxa1^tm3.1Mrc Hoxb1^tm3Mrc/Hoxb1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3773292
cx5	Hoxa1^tm3.1Mrc/Hoxa1^tm4(Hoxb1)Mrc Hoxb1^tm5Mrc/Hoxb1^tm8(Hoxa1)Mrc	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6	MGI:3703012

Genotype
MGI:3773293

hm1

• Allelic Composition: Hoxa1^tm3.1Mrc/Hoxa1^tm3.1Mrc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

perinatal lethality, complete penetrance ( J:178887 )

• pups die at P0-P1

cardiovascular system

abnormal cardiovascular system morphology ( J:178887 )

• 74% of mutants exhibit cardiovascular defects at E18.5-P1

abnormal aortic arch morphology ( J:178887 )

• 68% of mutants exhibit aortic arch malformations

• aortic arch malformations are the most severe cardiovascular defects in mutants

retroesophageal right subclavian artery ( J:178887 )

• 18% of mutants exhibit aberrant retroesophageal right subclavian artery

interrupted aortic arch, type b ( J:178887 )

• 50% of mutants exhibit interrupted aortic arch type B (IAAB)

right aortic arch ( J:178887 )

• 3% of mutants exhibit right aortic arch

abnormal external carotid artery morphology ( J:178887 )

• 68% of mutants exhibit cerebrovascular abnormalities including abnormal branching, hypoplasia or aplasia of the internal and external carotid arteries

abnormal internal carotid artery morphology ( J:178887 )

• 68% of mutants exhibit cerebrovascular abnormalities including abnormal branching, hypoplasia or aplasia of the internal and external carotid arteries

heart right ventricle hypertrophy ( J:178887 )

• two mutants with ventricular septal defect exhibit overriding aorta, pulmonary stenosis and hypertrophy of the right ventricle, hallmarks of Tetralogy of Fallot

abnormal cardiac outflow tract development ( J:178887 )

• 47% of mutants exhibit cardiac outflow tract abnormalities

overriding aortic valve ( J:178887 )

• two mutants with ventricular septal defect exhibit overriding aorta, pulmonary stenosis and hypertrophy of the right ventricle, hallmarks of Tetralogy of Fallot

ventricular septal defect ( J:178887 )

• seen in 24% of mutants

bicuspid aortic valve ( J:178887 )

• seen in 24% of mutants

nervous system

increased hindbrain apoptosis ( J:41540 )

• apoptosis in the hindbrain is increased

embryo

small second pharyngeal arch ( J:41540 )

• hypoplasia of the second branchial arch is barely perceptible

endocrine/exocrine glands

abnormal gland morphology ( J:178887 )

• all mutants show at least one cardiovascular or glandular malformation

absent parathyroid glands ( J:178887 )

• 71% of mutants exhibit parathyroid hypoplasia or aplasia

parathyroid hypoplasia ( J:178887 )

• 71% of mutants exhibit parathyroid hypoplasia or aplasia

thymus hypoplasia ( J:178887 )

• 71% of mutants exhibit thymic hypoplasia

hematopoietic system

thymus hypoplasia ( J:178887 )

• 71% of mutants exhibit thymic hypoplasia

immune system

thymus hypoplasia ( J:178887 )

• 71% of mutants exhibit thymic hypoplasia

craniofacial

small second pharyngeal arch ( J:41540 )

• hypoplasia of the second branchial arch is barely perceptible

muscle

heart right ventricle hypertrophy ( J:178887 )

• two mutants with ventricular septal defect exhibit overriding aorta, pulmonary stenosis and hypertrophy of the right ventricle, hallmarks of Tetralogy of Fallot

cellular

increased hindbrain apoptosis ( J:41540 )

• apoptosis in the hindbrain is increased

growth/size/body

heart right ventricle hypertrophy ( J:178887 )

• two mutants with ventricular septal defect exhibit overriding aorta, pulmonary stenosis and hypertrophy of the right ventricle, hallmarks of Tetralogy of Fallot

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Athabaskan brainstem dysgenesis syndrome		DOID:0050682	OMIM:601536	J:178887

Genotype
MGI:3703013

ht2

• Allelic Composition: Hoxa1^tm3.1Mrc/Hoxa1^{tm4(Hoxb1)Mrc}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

abnormal reflex ( J:119279 )

• in response to an air puff, mice display defects ranging from complete inability to operate eyelids to mild defects where only a narrow slit remains open; 72% of animals are severely affected

• all animals were unable to completely close eyelids (eyeblink reflex) on at least one side

• 44% of mutants exhibit unilateral constraint of most anterior whisking range in response to air puff stimulus

• 7% exhibited one-sided weakness of pinna retraction in response to stimulus

facial paralysis ( J:119279 )

• mice show completely penetrant partial facial paralysis

nervous system

abnormal facial nerve morphology ( J:119279 )

• in mice with a severe eyeblink defect, zygomatic branch of facial nerve is exceedingly thin or absent; sometimes the nerve takes an aberrant trajectory

Genotype
MGI:3773291

cx3

• Allelic Composition: Hoxa1^tm3.1Mrc/Hoxa1^tm3.1Mrc; Hoxb1^tm3Mrc/Hoxb1^tm3Mrc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

increased hindbrain apoptosis ( J:41540 )

• apoptosis in the hindbrain is increased and extends more posteriorly than in Hoxa1 null mice

abnormal neuron differentiation ( J:41540 )

• branchiomotor neurons do not fasciculate and exit at multiple points along the neural tube unlike in wild-type mice

abnormal rhombomere morphology ( J:41540 )

• hindbrain organization into even- and odd-numbered rhombomeres is lacking

• molecular markers reveal a lack of rhombomeres 4 and 5

absent rhombomere 4 ( J:41540 )

absent rhombomere 5 ( J:41540 )

vision/eye

absent orbicularis oculi muscle ( J:41540 )

• mice lack the orbicularis occuli muscle

embryo

abnormal neural crest cell migration ( J:41540 )

absent second pharyngeal arch ( J:41540 )

abnormal rhombomere morphology ( J:41540 )

• hindbrain organization into even- and odd-numbered rhombomeres is lacking

• molecular markers reveal a lack of rhombomeres 4 and 5

absent rhombomere 4 ( J:41540 )

absent rhombomere 5 ( J:41540 )

absent second pharyngeal pouch ( J:41540 )

• the second branchial pouch is absent

abnormal third pharyngeal pouch morphology ( J:41540 )

• the shape of the third pharyngeal pouch is distorted

craniofacial

small incus ( J:41540 )

• the incus is reduced in size

small malleus ( J:41540 )

absent stapes ( J:41540 )

• the stapes derived from the second branchial arch is absent

absent second pharyngeal arch ( J:41540 )

absent orbicularis oculi muscle ( J:41540 )

• mice lack the orbicularis occuli muscle

absent facial muscle ( J:41540 )

• mice lack the levator labii maxillaris, orbicularis occuli and zygomatic muscles

absent levator labii superioris muscle ( J:41540 )

• mice lack the levator labii maxillaris

absent zygomaticus muscle ( J:41540 )

• mice lack the zygomatic muscles

endocrine/exocrine glands

absent parathyroid glands ( J:41540 )

athymia ( J:41540 )

hearing/vestibular/ear

small incus ( J:41540 )

• the incus is reduced in size

small malleus ( J:41540 )

absent stapes ( J:41540 )

• the stapes derived from the second branchial arch is absent

respiratory system

abnormal digastric posterior belly morphology ( J:41540 )

• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle

abnormal stylohyoid muscle morphology ( J:41540 )

• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle

pulmonary hypoplasia ( J:41540 )

• at birth, mice exhibit lung hypoplasia that ranges from 5 small lobes to the presence of only two lobes

muscle

absent orbicularis oculi muscle ( J:41540 )

• mice lack the orbicularis occuli muscle

absent facial muscle ( J:41540 )

• mice lack the levator labii maxillaris, orbicularis occuli and zygomatic muscles

absent levator labii superioris muscle ( J:41540 )

• mice lack the levator labii maxillaris

absent zygomaticus muscle ( J:41540 )

• mice lack the zygomatic muscles

abnormal digastric posterior belly morphology ( J:41540 )

• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle

abnormal stylohyoid muscle morphology ( J:41540 )

• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle

immune system

athymia ( J:41540 )

skeleton

small incus ( J:41540 )

• the incus is reduced in size

small malleus ( J:41540 )

absent stapes ( J:41540 )

• the stapes derived from the second branchial arch is absent

hematopoietic system

athymia ( J:41540 )

cellular

increased hindbrain apoptosis ( J:41540 )

• apoptosis in the hindbrain is increased and extends more posteriorly than in Hoxa1 null mice

abnormal neuron differentiation ( J:41540 )

• branchiomotor neurons do not fasciculate and exit at multiple points along the neural tube unlike in wild-type mice

abnormal neural crest cell migration ( J:41540 )

growth/size/body

absent orbicularis oculi muscle ( J:41540 )

• mice lack the orbicularis occuli muscle

absent facial muscle ( J:41540 )

• mice lack the levator labii maxillaris, orbicularis occuli and zygomatic muscles

absent levator labii superioris muscle ( J:41540 )

• mice lack the levator labii maxillaris

absent zygomaticus muscle ( J:41540 )

• mice lack the zygomatic muscles

Genotype
MGI:3773292

cx4

• Allelic Composition: Hoxa1^tm3.1Mrc/Hoxa1^tm3.1Mrc; Hoxb1^tm3Mrc/Hoxb1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal neuron differentiation ( J:41540 )

• branchiomotor neurons do not fasciculate and exit at multiple points along the neural tube unlike in wild-type mice

abnormal rhombomere morphology ( J:41540 )

• hindbrain organization into even- and odd-numbered rhombomeres is lacking

embryo

abnormal neural crest cell migration ( J:41540 )

absent second pharyngeal arch ( J:41540 )

abnormal rhombomere morphology ( J:41540 )

• hindbrain organization into even- and odd-numbered rhombomeres is lacking

abnormal pharyngeal pouch morphology ( J:41540 )

• some mice exhibit a distortion of the second and third pouch towards the first

craniofacial

absent second pharyngeal arch ( J:41540 )

endocrine/exocrine glands

absent parathyroid glands ( J:41540 )

small thymus ( J:41540 )

hematopoietic system

small thymus ( J:41540 )

immune system

small thymus ( J:41540 )

cellular

abnormal neuron differentiation ( J:41540 )

• branchiomotor neurons do not fasciculate and exit at multiple points along the neural tube unlike in wild-type mice

abnormal neural crest cell migration ( J:41540 )

Genotype
MGI:3703012

cx5

• Allelic Composition: Hoxa1^tm3.1Mrc/Hoxa1^{tm4(Hoxb1)Mrc}; Hoxb1^tm5Mrc/Hoxb1^{tm8(Hoxa1)Mrc}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6

behavior/neurological

abnormal blinking ( J:119279 )

• facial paralysis is predominantly manifested in impaired eyeblink reflex

facial paralysis ( J:119279 )

• majority of mice show various levels of facial paralysis