Mouse Genome Informatics
hm1
    Pax6Sey/Pax6Sey
B10.Cg-Pax6Sey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are still viable at E11.5 but are seldom born

vision/eye
• fail to develop eye pigment by E11.5 in mice that lack the lens
• at E10.5, mice lack lenses
• however, optic vessicles are normal in size

nervous system
• at birth

respiratory system
• at E10.5, mice lack the nasal pit

craniofacial
• only small frontonasal protuberances formed by E11.5 which later fuse with maxillary processes
• at E10.5, mice lack the nasal pit

pigmentation
• fail to develop eye pigment by E11.5 in mice that lack the lens

skeleton
• only small frontonasal protuberances formed by E11.5 which later fuse with maxillary processes


Mouse Genome Informatics
hm2
    Pax6Sey/Pax6Sey
C.Cg-Pax6Sey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• animals show corneal edema with deranged collagen bundles
• corneal epithelium has a bubbly appearance like Foxe3tm1Pca /+ or Foxe3dyl /+ mice

cardiovascular system


Mouse Genome Informatics
hm3
    Pax6Sey/Pax6Sey
CBACa.Cg-Pax6Sey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
N
• mice do not possess supernumerary incisors (J:43913)
• all mice exhibit a median cartilaginous rod unlike wild-type mice
• 33% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• unlike in wild-type mice the nasal capsule surrounds the entire are of the developing incisor teeth

respiratory system
• 33% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• unlike in wild-type mice the nasal capsule surrounds the entire are of the developing incisor teeth

skeleton
• all mice exhibit a median cartilaginous rod unlike wild-type mice
• 33% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• unlike in wild-type mice the nasal capsule surrounds the entire are of the developing incisor teeth

growth/size
• 33% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• unlike in wild-type mice the nasal capsule surrounds the entire are of the developing incisor teeth


Mouse Genome Informatics
hm4
    Pax6Sey/Pax6Sey
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die soon after birth because of inability to breathe during suckling

vision/eye
• at E15, homozygotes have no visible eyes

craniofacial
• defects in nasal cavity development results in shortened, imperforate snout

respiratory system

growth/size
• defects in nasal cavity development results in shortened, imperforate snout


Mouse Genome Informatics
hm5
    Pax6Sey/Pax6Sey
involves: C57BL/6J * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• decrease in the number of neurons generated in the cerebral cortex
• 2.4 fold increase in subventricular zone precursors but not in ventricular zone precursors of the cortex
• at E14, proliferation of marginal zone neural progenitors of the cerebral cortex is increased three time compared to in wild-type mice
• altered dorso-ventral patterning of the forebrain
• altered dorso-ventral telencephalic boundary
• decreased thickness of the cortical plate
• 2.4 fold increase in subventricular zone precursors but not in ventricular zone precursors of the cortex

cellular
• decrease in the number of neurons generated in the cerebral cortex
• 2.4 fold increase in subventricular zone precursors but not in ventricular zone precursors of the cortex


Mouse Genome Informatics
hm6
    Pax6Sey/Pax6Sey
involves: ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E18.5, mice display a teardrop shaped cerebellum due to thinning of the cerebellar vermis and thickening of the lateral hemisphere in addition to alterations in the medial to lateral profile of areas from sagittal sections
• the external granule cell layer area is increased compared to wild-type
• Purkinje cells are located abnormally deep compared to in wild-type mice
• ectopic Purkinje cells are located in the distinct clusters in the vermis and hemisphere and in the inferior colliculus
• 25% of Purkinje cells are located deep to the developing Purkinje cell plate compared to only 3% in wild-type mice
• in culture, granule cells exhibit increased numbers of cellular aggregates due to increased proliferation
• the vermis is thinned


Mouse Genome Informatics
hm7
    Pax6Sey/Pax6Sey
involves: Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• absence of lens placode and lens pit
• broader rather than proximally constricted at E9.5
• optic stalk retains a lumen through E15.5
• contact of optic vesicle with surface ectoderm at E9.5 but progressively lost as mesenchymal cells intervene

respiratory system
• lateral nasal processes absent at E10.5
• nasal placodes not detectable at E9.5

taste/olfaction
• nasal placodes not detectable at E9.5

craniofacial
• nasal placodes not detectable at E9.5


Mouse Genome Informatics
hm8
    Pax6Sey/Pax6Sey
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• develop to term but die of breathing problems associated with the lack of a nose

vision/eye

nervous system
• at E10.5 Nkx2.2+ V3 progenitors show dorsal expansion in the thoracic and cervical regions of the spinal cord
• anterior pretectum is reduced but present and the posterior pretectum scarcely exists at E12.5
• diencephalic structures were poor but present
• prethalamus and thalamus were reduced at E12.5
• while apoptosis and proliferation rates are unchanged, a greater number of cells exit the cell cycle and differentiate than in wild-type mice
• at E12.5, 114+/-7.1 um compared to 135+/+6.2 um for wild-type cortex
• E17.5 mutants show a greater than 90% reduction in the number of calbindin-positive cells close to the white matter in the spinal cord, indicating that Renshaw cells fail to develop
• no synaptic potentials are evoked by ventral root stimulation, indicating that Renshaw cell inputs to motor neurons are absent

respiratory system
• due to lack of nose
• cause of perinatal death

craniofacial

cellular
• at E10.5 Nkx2.2+ V3 progenitors show dorsal expansion in the thoracic and cervical regions of the spinal cord

growth/size


Mouse Genome Informatics
ht9
    Pax6Sey/Pax6+
B10.Cg-Pax6Sey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• sometimes folding around anterior of lense
• with many vacuolated cells
• sometimes incompletely separated from overlying ectoderm

pigmentation
• sometimes folding around anterior of lense


Mouse Genome Informatics
ht10
    Pax6Sey/Pax6+
C.Cg-Pax6Sey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• at E11.5, lens pit or vesicle is smaller than in wild-type
• reduction in lens vesicle tissue volume is similar to that observed in Foxe3dyl homozygotes, while in Foxe3-heterozygotes volume reduction is intermediate between homozygotes and wild-type


Mouse Genome Informatics
ht11
    Pax6Sey/Pax6+
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• at E15, fissure of optic cup is often delayed in closing
• at E15, there is folding at the margin of the optic cup resulting in a keyhole-shaped opening
• at E15 heterozygotes have smaller eyes than wild-type


Mouse Genome Informatics
ht12
    Pax6Sey/Pax6+
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Development of the Pax6Sey/Pax6+ lens

vision/eye
• myelinated nerve counts lower than in controls
• cross sectional area in males significantly smaller than in controls
• display a persistent plug of ectoderm linking the corneal and anterior lens epithelia at E16.6
• the lens-corneal bridge exhibits high levels of apoptosis but normal proliferation
• reduced anterior chamber, with multiple sites of adhesion between the anterior surface of the lens and the corneal endothelium
• the lens shows evidence of degeneration
• the lens is developmentally delayed
• persistence of the lens vesicular cavity
• extensive vacuolation of the primary lens fibers
• delayed fusion of the eyelids
• microphthalmia, but highly variable from almost unnoticeable to very small (J:12101)
• never anophthalmic (J:12101)
• frequently necrotic in adults
• sensory cells in only 15% of eyes

growth/size
• reduced size

nervous system
• myelinated nerve counts lower than in controls
• cross sectional area in males significantly smaller than in controls

pigmentation
• frequently necrotic in adults

Mouse Models of Human Disease
OMIM IDRef(s)
Aniridia; AN 106210 J:22316
Peters Anomaly 604229 J:22316


Mouse Genome Informatics
ht13
    Pax6Sey/Pax6Sey-H
involves: 101/H * C3H/HeH * C57BL/10
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• at E13.5, the maxillae are not fused and there is only a small bilobed protrusion in the frontonasal position that in some mice may fuse on one side
• facial development is retarded compared to wild-type and Pax6Sey homozygotes

vision/eye
• while small bleds are present in the area occupied by the eye they contain no brain involvement

embryogenesis
• at E13.5, mice are smaller than wild-type and Pax6sey homozygotes

skeleton
• at E13.5, the maxillae are not fused and there is only a small bilobed protrusion in the frontonasal position that in some mice may fuse on one side

digestive/alimentary system
• at E13.5, the maxillae are not fused and there is only a small bilobed protrusion in the frontonasal position that in some mice may fuse on one side

growth/size
• at E13.5, the maxillae are not fused and there is only a small bilobed protrusion in the frontonasal position that in some mice may fuse on one side
• at E13.5, mice are smaller than wild-type and Pax6sey homozygotes


Mouse Genome Informatics
ht14
    Pax6Sey-Dey/Pax6Sey
involves: C3H/HeJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• 23% of embryos from a heterozygous intercross show not development of nasal placodes

taste/olfaction
• 23% of embryos from a heterozygous intercross show not development of nasal placodes

vision/eye
• 23% of embryos from a heterozygous intercross show no development of the lens
• approximately a third of the embryos 14.5 days or older from heterozygous intercrosses are colobomatous

craniofacial
• 23% of embryos from a heterozygous intercross show not development of nasal placodes


Mouse Genome Informatics
cx15
    Pax6Sey/Pax6Sey-Neu
Tg(Hbb-b1)83Clo/0

involves: 102 * C3H * C57BL * CBA/Ca * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• all mice exhibit a median cartilaginous rod unlike wild-type mice
• 22% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• 22% of mice possess a single supernumerary upper incisor tooth

respiratory system
• 22% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule

skeleton
• all mice exhibit a median cartilaginous rod unlike wild-type mice
• 22% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule

growth/size
• 22% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• 22% of mice possess a single supernumerary upper incisor tooth


Mouse Genome Informatics
cx16
    Gli2tm1Alj/Gli2tm1Alj
Pax6Sey/Pax6Sey

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
• at E10.5 Nkx2.2+ V3 progenitors show dorsal expansion in the thoracic region similar to Pax6 single homozygotes

cellular
• at E10.5 Nkx2.2+ V3 progenitors show dorsal expansion in the thoracic region similar to Pax6 single homozygotes


Mouse Genome Informatics
cx17
    Pax6Sey/Pax6Sey
Tg(Hbb-b1)83Clo/0

involves: C57BL * CBA/Ca * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• all mice exhibit a median cartilaginous rod unlike wild-type mice
• 86% mice from the agouti sub-line, but none from the non-agouti sub-line, posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• 43% of mice from the agouti sub-line exhibit supernumerary upper incisor teeth and 14% of the non-agouti line possess a single supernumerary upper incisor tooth

respiratory system
• 86% mice from the agouti sub-line, but none from the non-agouti sub-line, posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule

skeleton
• all mice exhibit a median cartilaginous rod unlike wild-type mice
• 86% mice from the agouti sub-line, but none from the non-agouti sub-line, posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule

growth/size
• 86% mice from the agouti sub-line, but none from the non-agouti sub-line, posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule
• 43% of mice from the agouti sub-line exhibit supernumerary upper incisor teeth and 14% of the non-agouti line possess a single supernumerary upper incisor tooth


Mouse Genome Informatics
cx18
    Emx2tm1Sia/Emx2tm1Sia
Pax6Sey/Pax6Sey

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• an amorphous structure was present where normally the thalamus/pretectum develops at E12.5
• the supraopto-paraventricular area was lost at E12.5
• choroid plexus was never apparent at E12.5
• the commissural plate was caudally expanded
• mirror image duplication of tectum at E18.5, however duplication of the cerebellum or tegmentum did not occur
• both the non-commissure region and the commissure region of the pretectum were absent at E12.5
• prethalamus and thalamus were not apparent at E12.5
• zona limitans intrathalamica was never formed
• diencephalic structures were not apparent at E12.5
• the choroidal roof at the telencephalic level did not develop
• Ammon's horn did not develop at E12.5
• prospective hippocampus was absent at E12.5
• greatly reduced pallium at E18.5 that was lost in the medial portion, greatly reduced but present neopallium at E12.5 and absent cortical hem at E12.5
• hyperplastic ganglionic eminences


Mouse Genome Informatics
cx19
    Pax6Sey/Pax6Sey
Tg(PAX6)77Ndha/?

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
N
• normal eye size (J:34194)

taste/olfaction
N
• nasal cavity present (J:34194)
• normal olfactory epithelium (J:34194)

nervous system
N
• olfactory bulbs normal (J:34194)
• subventricular zone of cerebral hemispheres normal (J:34194)