Mouse Genome Informatics
hm1
    Pax6Sey-Neu/Pax6Sey-Neu
CBACa.Cg-Pax6Sey-Neu
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
• 27% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule

respiratory system
• 27% 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
• 27% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule

growth/size
• 27% of mice posses unilateral or bilateral ectopic cartilaginous spurs derived from the antero-lateral aspect of the nasal capsule


Mouse Genome Informatics
hm2
    Pax6Sey-Neu/Pax6Sey-Neu
involves: 102 * C3H
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die at birth

homeostasis/metabolism
• at E17.5 and P0, growth hormone levels are 5-fold and 3-fold lower, respectively, than in wild-type mice

nervous system
• the posterior commissure is smaller than in wild-type mice
• at E10.5, the hemispheric sulcus is absent
• olfactory nerves are absent

vision/eye
• at E10.5, the optic vesicle is overly broad

taste/olfaction
• unlike in wild-type mice, only bilateral, small and irregular clusters of epithelial vesicle cells are observed where the olfactory epithelium should be located

digestive/alimentary system
• mice exhibit disorganized mesenchyme
• mice exhibit hypoplastic submandibular glands

endocrine/exocrine glands
• mice exhibit disorganized mesenchyme
• mice exhibit hypoplastic submandibular glands

respiratory system
• unlike in wild-type mice, only bilateral, small and irregular clusters of epithelial vesicle cells are observed where the olfactory epithelium should be located

craniofacial
• unlike in wild-type mice, only bilateral, small and irregular clusters of epithelial vesicle cells are observed where the olfactory epithelium should be located

growth/size
• unlike in wild-type mice, only bilateral, small and irregular clusters of epithelial vesicle cells are observed where the olfactory epithelium should be located


Mouse Genome Informatics
hm3
    Pax6Sey-Neu/Pax6Sey-Neu
involves: 102 * C3H * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• at E18.5, the amount of glucagon in the pancreas is 2.6% of wild-type (13.8+/-1.45 ng/mg protein compared to 527+/-62.8 ng/mg protein in wild-type)
• at E18.5, the amount of insulin in the pancreas is 13% of wild-type (1.6+/-0.08 ug/mg protein compared to 12.2+/-1.3 ug/mg protein in wild-type)

nervous system
• at E10.5 to E12.5, pallium development is abnormal such that pallial subdivisions closets to the pallial/subpallial boundary are most severely affected as determined by the expression several markers
• the ventral pallium progenitor zone becomes more ventralized

endocrine/exocrine glands
• at E12.5, no alpha or beta cells are detected
• at E18.5, no glucagons producing cells are detected
• at E12.5, no alpha or beta cells are detected


Mouse Genome Informatics
hm4
    Pax6Sey-Neu/Pax6Sey-Neu
involves: 102 * C3H * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye

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
hm5
    Pax6Sey-Neu/Pax6Sey-Neu
involves: 102/El * C3H/Rl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• there is a significant reduction in the number of cells expressing insulin and glucagon in the pancreas of E15.5 embyros
• the number of insulin-positive cells is still low at E17.5
• the number of glucagon expressing cells is lower than wild-type at E12.5


Mouse Genome Informatics
ht6
    Pax6Sey-Neu/Pax6+
C3.Cg-Pax6Sey-Neu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• eye placode development is delayed
• mice exhibit reduced numbers of lens cells compared to wild-type mice (49+/-5% fewer at E10.5, 56+/-6% fewer at E11.5, and 46+/-3% at E12.5)


Mouse Genome Informatics
ht7
    Pax6Sey-Neu/Pax6+
involves: 102 * C3H
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• at E18.5, the iris is hypoplastic and the iridocorneal angle is obliterated by cells
• the lens stalk persists and forms an epithelial plug in the cornea
• corneal degeneration worsens with age with older mice exhibiting more prominent subepithelial pannus and more goblet cells than younger mice
• many mice develop vascularized cornea or ones that contain cellular infiltrates unlike in wild-type mice (J:83026)
• mice exhibited spontaneous corneal vascularization (J:114973)
• corneal injection of sflt-1 (secreted isoform of the cell surface receptor membrane-bound Flt1) protein reduces the area of vascularization compared to untreated mutant mice (J:114973)
• keratolenticular adhesions are present in the central cornea and between the anterior iris stroma and trabecullar meshwork between the iris stroma and the peripheral cornea, and between extensions of abnormal iris processes and the cornea
• at P14, Bowman's layer is interrupted in some areas
• unlike in wild-type mice, the lens vesicle remains attached to the surface of the corneal epithelium by a persistent lens stalk (J:83026)
• at P14, the corneal epithelium is thinner (2 to 3 cell layers thick compared to 3 to 4 cell layers thick in wild-type mice) (J:83026)
• reduction in cell layers is apparent at P14 and P21 (J:83791)
• unlike in wild-type mice, basal cells are more rounded and the cell layers are not packed tightly (J:83791)
• no goblet cells are observed (J:83791)
• the corneal epithelium is 1 to 7 cell layers thick instead of 8 to 10 as in wild-type mice (J:83791)
• however, apoptosis rates are normal (J:83791)
• adhesion between cells in the suprabasal middle and superficial layers is disrupted (J:83791)
• at E16.5 and E18.5, the stroma appears thicker and parallel arrangement is distorted toward the center of the cornea (J:83026)
• the stroma exhibits varied thickness and a general disorganizeation with large aggregates of laminn in the anterior region (J:83791)
• hypercellular at fetal stages
• the anterior stroma sometimes appears edematous and in 2 of 4 mice the formation of pannus occurs in the superficial stroma
• by E14.5, the anterior chamber has not formed unlike in wild-type mice
• at E16.5, the center of the anterior chamber is interrupted by a persistent lens stalk
• unlike in wild-type mice, the lens vesicle remains attached to the surface of the corneal epithelium by a persistent lens stalk
• eye weight is decreased (16.0+/-0.3 mg compared to 21.4+/-0.3 mg in wild-type mice)

cardiovascular system
• many mice develop vascularized cornea or ones that contain cellular infiltrates unlike in wild-type mice (J:83026)
• mice exhibited spontaneous corneal vascularization (J:114973)
• corneal injection of sflt-1 (secreted isoform of the cell surface receptor membrane-bound Flt1) protein reduces the area of vascularization compared to untreated mutant mice (J:114973)


Mouse Genome Informatics
ht8
    Pax6Sey-Neu/Pax6+
involves: 102 * C3H * C3H/HeN
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 dysmorphia is observed


Mouse Genome Informatics
ht9
    Pax6Sey-Neu/Pax6tm1.1Zkoz
involves: 102/El * C3H/Rl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• slight delay in optic cup morphogenesis at E10.5


Mouse Genome Informatics
cn10
    Pax6tm1.1Zkoz/Pax6Sey-Neu
Tg(Rax-cre)1Zkoz/0

involves: 102/El * C3H/Rl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• does not form lens vesicle at E11
• optic vesicle arrests at E11 or shows only a small invagination into an optic cup like structure
• at E11
• defective lens/optic cup formation at E11


Mouse Genome Informatics
cx11
    Pax6Sey-Neu/Pax6+
Sox2tm1.1Vep/Sox2+

involves: 102 * C3H * C3H/HeN
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 dysmorphia is observed but is no more severe than in Pax6Sey-Neu heterozygotes


Mouse Genome Informatics
cx12
    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
cx13
    Mitftm3.1Arnh/Mitftm3.1Arnh
Pax6Sey-Neu/Pax6+

involves: 129S6/SvEvTac * C57BL/6N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• dorsal thickening observed at E11.5 becoming prominent at E13.5
• trans-differentiating retinal pigment epithelium cells generate differentiated retinal cells by birth

pigmentation
• dorsal thickening observed at E11.5 becoming prominent at E13.5
• trans-differentiating retinal pigment epithelium cells generate differentiated retinal cells by birth


Mouse Genome Informatics
cx14
    Mitfmi-vga9/Mitf+
Pax6Sey-Neu/Pax6+

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
• dorsal thickening observed at E13.5

pigmentation
• dorsal thickening observed at E13.5


Mouse Genome Informatics
cx15
    Mitfmi-vga9/Mitfmi-vga9
Pax6Sey-Neu/Pax6Sey-Neu

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
• massive enlargement of the retinal pigment epithelium at E13.5

pigmentation
• massive enlargement of the retinal pigment epithelium at E13.5


Mouse Genome Informatics
cx16
    Mitfmi-vga9/Mitfmi-vga9
Pax6Sey-Neu/Pax6+

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
• trans-differentiating retinal pigment epithelium cells generate differentiated retinal cells by birth

pigmentation
• trans-differentiating retinal pigment epithelium cells generate differentiated retinal cells by birth