Mouse Genome Informatics
hm1
    Hoxa1tm3.1Mrc/Hoxa1tm3.1Mrc
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• pups die at P0-P1

cardiovascular system
• 74% of mutants exhibit cardiovascular defects at E18.5-P1
• 68% of mutants exhibit aortic arch malformations
• aortic arch malformations are the most severe cardiovascular defects in mutants
• 18% of mutants exhibit aberrant retroesophageal right subclavian artery
• 50% of mutants exhibit interrupted aortic arch type B (IAAB)
• 3% of mutants exhibit right aortic arch
• 68% of mutants exhibit cerebrovascular abnormalities including abnormal branching, hypoplasia or aplasia of the internal and external carotid arteries
• 68% of mutants exhibit cerebrovascular abnormalities including abnormal branching, hypoplasia or aplasia of the internal and external carotid arteries
• 47% of mutants exhibit cardiac outflow tract abnormalities
• two mutants with ventricular septal defect exhibit overriding aorta, pulmonary stenosis and hypertrophy of the right ventricle, hallmarks of Tetralogy of Fallot
• seen in 24% of mutants
• two mutants with ventricular septal defect exhibit overriding aorta, pulmonary stenosis and hypertrophy of the right ventricle, hallmarks of Tetralogy of Fallot
• seen in 24% of mutants

nervous system
• apoptosis in the hindbrain is increased

embryogenesis
• hypoplasia of the second branchial arch is barely perceptible

endocrine/exocrine glands
• all mutants show at least one cardiovascular or glandular malformation
• 71% of mutants exhibit parathyroid hypoplasia or aplasia
• 71% of mutants exhibit parathyroid hypoplasia or aplasia
• 71% of mutants exhibit thymic hypoplasia

hematopoietic system
• 71% of mutants exhibit thymic hypoplasia

immune system
• 71% of mutants exhibit thymic hypoplasia

craniofacial
• hypoplasia of the second branchial arch is barely perceptible

Mouse Models of Human Disease
OMIM IDRef(s)
Athabaskan Brainstem Dysgenesis Syndrome; ABDS 601536 J:178887


Mouse Genome Informatics
ht2
    Hoxa1tm3.1Mrc/Hoxa1tm4(Hoxb1)Mrc
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• mice show completely penetrant partial facial paralysis

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


Mouse Genome Informatics
cx3
    Hoxa1tm3.1Mrc/Hoxa1tm3.1Mrc
Hoxb1tm3Mrc/Hoxb1tm3Mrc

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• branchiomotor neurons do not fasciculate and exit at multiple points along the neural tube unlike in wild-type mice
• hindbrain organization into even- and odd-numbered rhombomeres is lacking
• molecular markers reveal a lack of rhombomeres 4 and 5
• apoptosis in the hindbrain is increased and extends more posteriorly than in Hoxa1 null mice

embryogenesis
• hindbrain organization into even- and odd-numbered rhombomeres is lacking
• molecular markers reveal a lack of rhombomeres 4 and 5
• the second branchial pouch is absent and the shape of the third is distorted

craniofacial
• the incus is reduced in size
• the stapes derived from the second branchial arch is absent
• mice lack the levator labii maxillaries, orbicularis occuli and zygomatic muscles
• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle

endocrine/exocrine glands

hearing/vestibular/ear
• the incus is reduced in size
• the stapes derived from the second branchial arch is absent

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

muscle
• mice lack the levator labii maxillaries, orbicularis occuli and zygomatic muscles
• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle

immune system

skeleton
• the incus is reduced in size
• the stapes derived from the second branchial arch is absent

hematopoietic system

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

growth/size
• mice lack the levator labii maxillaries, orbicularis occuli and zygomatic muscles
• the posterior belly of the digastric and stylohyoid muscles form but act as a single muscle


Mouse Genome Informatics
cx4
    Hoxa1tm3.1Mrc/Hoxa1tm3.1Mrc
Hoxb1tm3Mrc/Hoxb1+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• branchiomotor neurons do not fasciculate and exit at multiple points along the neural tube unlike in wild-type mice
• hindbrain organization into even- and odd-numbered rhombomeres is lacking

embryogenesis
• hindbrain organization into even- and odd-numbered rhombomeres is lacking
• some mice exhibit a distortion of the second and third pouch towards the first

craniofacial

endocrine/exocrine glands

hematopoietic system

immune system

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


Mouse Genome Informatics
cx5
    Hoxa1tm3.1Mrc/Hoxa1tm4(Hoxb1)Mrc
Hoxb1tm5Mrc/Hoxb1tm8(Hoxa1)Mrc

involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• facial paralysis is predominantly manifested in impaired eyeblink reflex
• majority of mice show various levels of facial paralysis