Mouse Genome Informatics
hm1
    En2tm1Alj/En2tm1Alj
either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• abnormal folding of the paraflocculus (J:31921)
• fused folds in the hemispheres results in 3 rather than 4 lobules (J:31921)
• reduction of Crus I and Crus II (J:67524)
• reduced paraflocculus (J:67524)
• altered pattern (J:67524)
• extended tuber vermis or pyramis
• abnormal folding of the posterior vermis
• size reductions and delayed midline fusion observed embryonically (J:31921)
• reduced in size at 8 weeks of age (J:67524)

behavior/neurological
• improvement in performance with initial testing on a rotarod but improvement is less with later testing
• less habituation observed in locomotor activity tests

digestive/alimentary system
• observed in open field and bar cross behavior tests


Mouse Genome Informatics
hm2
    En2tm1Alj/En2tm1Alj
involves: 129/Sv * 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• reduced in size by E15.5-E16.5
• cerebellar anlage slightly reduced in size at E13.5
• anlage clearly reduced in size at E15.5 and E16.5 and midline fusions are reduced
• apparently normal cerebellum at E17.5
• altered pattern
• failure of ansoparamedial fissure to form resulting of fusion of crus II with paramedial lobule
• 3 rather than 4 major folds
• external granular layer is decreased in thickness between E15 and 9 days of age
• delayed formation of inner granular layer
• delayed foliation
• anterior region tends to develop normally
• precentral fissure fails to form until age 6 days
• posterolateral fissure only posterior region fissure present at birth
• formation of remaining posterior fissures abnormal
• lobe IX is abnormal in shape


Mouse Genome Informatics
hm3
    En2tm1Alj/En2tm1Alj
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• reduced allogrooming among juveniles
• increased allogrooming among males rather than aggressive behavior
• deficient performance in a hidden platform test
• while falling but not on a flat surface
• poor performance on rotarod tests
• from age 21-27 days
• latency to attack is increased in adult males
• significantly reduced social interactions (play) in juveniles
• hypoactivity
• less sniffing

homeostasis/metabolism
• increased serotonin in the cerebellum
• increased 5-hydroxyindolacetic acid in the cerebellum

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:114464


Mouse Genome Informatics
ht4
    En2tm1Alj/En2+
either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• moderate behavioral impairment


Mouse Genome Informatics
cn5
    En1tm1Alj/En1tm8.1Alj
En2tm1Alj/En2tm7.1Alj
Gt(ROSA)26Sortm1(cre/ERT2)Alj/Gt(ROSA)26Sor+

involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• when given tamoxifen at E13.5 or E14. the hemisphere phenotype is more severe than in double mutants that do not express Cre
• when given tamoxifen at E13.5 or E14. the vermis phenotype is more severe than in double mutants that do not express Cre


Mouse Genome Informatics
cn6
    En2tm1Alj/En2tm6Alj
Gt(ROSA)26Sortm1(cre/ERT2)Alj/Gt(ROSA)26Sor+

involves: 129S2/SvPas * 129S6/SvEvTac * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice
• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice
• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice


Mouse Genome Informatics
cn7
    En1tm1Alj/En1tm8.1Alj
En2tm1Alj/En2tm6Alj
Gt(ROSA)26Sortm1(cre/ERT2)Alj/Gt(ROSA)26Sor+

involves: 129S2/SvPas * 129S6/SvEvTac * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen treatment at E9.5, but not at E10.5, results in death at birth

nervous system
• when tamoxifen treated at E10.5, at P2 proliferation is similar in the anterior and central lobules, unlike in wild-type mice
• a major deletion of the midbrain is seen when tamoxifen is given at E9.5, but not when given at E10.5
• a major deletion of the medial cerebellum is seen when tamoxifen is given at E9.5 but not when given at E10.5
• when given tamoxifen at E10.5, at P14 the distinction between the vermis and the hemispheres is not apparent
• when given tamoxifen at E10.5, at E12.5 the cerebellar primordium is reduced in size
• when tamoxifen treated at E10.5, development of the vermis prepyramidal fissure is delayed and the order of fissure initiation is altered
• when given tamoxifen at E10.5, at P14 cerebellar foliation patterns are disrupted
• when given tamoxifen at E13.5 or E14.5, foliation defects in adults are less severe than when tamoxifen is given at E10.5
• when tamoxifen treated at E10.5, at E18.5 the thickness of the external granule layer was 1.5-2 times greater in the mutants than in wild types
• when tamoxifen treated at E10.5, at P2 the thickness of the external granule layer is similar in the lobules IV/V and VI unlike in wild-type mice
• when tamoxifen treated at E10.5, at P2 thickness is similar to that at E18.5 and thinner than in the controls.
• when given tamoxifen at E13.5 or E14.5, in adults the preculminate fissure is absent (between I-II and III) as lobules I-III are fused
• when given tamoxifen at E10.5, at P3 the depth of the primary fissure is increased relative to the intercrural fissure
• when given tamoxifen at E10.5, at P14 the anterior region (lobules I-V) is reduced and the central region (lobules VI-VII) is preferentially expanded
• when tamoxifen is given at E10.5, at P14, unlike in wild type, the remnants of lobules I-V extend into the hemispheres
• when tamoxifen is given at E10.5, at P14 remnants of the vermis, specific anterior and posterior regions, are maintained more laterally than in wild-type
• when given tamoxifen at E10.5, at P14 in some mutants lobule VIII is diminished more medially than lobule IX rather than the opposite as occurs in wild-type
• when tamoxifen treated at E10.5, at P2 lobules I - V are smaller and lobule VI is much larger than in wild-type
• when tamoxifen is given at E13.5 or E14.5, in adults lobule VIII is shifted posterior and fused with dorsal lobule IX
• when tamoxifen treated at E10.5, at P2 the thickness of the external granule layer is similar in the lobules IV/V and VI unlike in wild-type mice
• when given tamoxifen at E10.5, at P14 lobules VI-VII occupy a greater proportion of the vermis than in wild-type
• when given tamoxifen at E10.5, at P14 lobules VIII-IX occupy a smaller proportion of the vermis than in wild-type
• when given tamoxifen at E13.5 or E14.5, in adults lobules I-III are fused into one lobule
• when tamoxifen treated at E10.5, at P2 overall size of each region, and thus total number of cells, is greatly reduced
• when given tamoxifen, at P3 the cerebellum is smaller compared to controls

cellular
• when tamoxifen treated at E10.5, at P2 proliferation is similar in the anterior and central lobules, unlike in wild-type mice


Mouse Genome Informatics
cx8
    En1tm1Gld/En1+
En2tm1Alj/En2tm1Alj

involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in the striatum
• loss of dopaminergic neurons specifically in the substantia nigra pars compacta starting after P0 and continuing until 3 months after birth
• loss is due to apoptosis, not conversion to another cell fate
• decreased in the release of dopamine from striatal slices following stimulation of the caudate putamen
• however, no defect in release is seen in the nucleus accumbens

behavior/neurological
• mice freeze more frequently while swimming compared to En2 null littermate controls
• between 5 and 11 weeks of age, mice consume less food per day compared to En2 null littermate controls
• decreased grip strength in an inverted grid assay compared to En2 null littermate controls at 8 months of age but not at 18 months of age
• however, at 18 months of age mice took fewer steps on the grid compared to En2 null littermate controls
• decrease in forward locomotion in an open field at 18 months of age but not at 8 months of age compared to En2 null littermate controls

growth/size
• beginning around 5 to 6 weeks of age

homeostasis/metabolism
• in the striatum


Mouse Genome Informatics
cx9
    En1tm1Gld/En1tm1Gld
En2tm1Alj/En2tm1Alj

involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• decrease in the number of mesencephalic dopaminergic neurons


Mouse Genome Informatics
cx10
    En1tm1Gld/En1tm1Gld
En2tm1Alj/En2+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• decrease in the number of mesencephalic dopaminergic neurons


Mouse Genome Informatics
cx11
    En1tm1Alj/En1tm8.1Alj
En2tm1Alj/En2tm7.1Alj

involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in the hemispheres, CrusII and Paramedian are only partially separated.
• in adults, only one or two major anterior lobules are present, and lobule VIII is very small and fused with dorsal lobule IX.


Mouse Genome Informatics
cx12
    En1tm1Alj/En1tm1Alj
En2tm1Alj/En2+

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system


Mouse Genome Informatics
cx13
    En1tm1Alj/En1+
En2tm1Alj/En2tm1Alj

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• normal cerebellum (J:84363)