Phenotypes associated with this allele

• Allele Symbol: En2^tm1Alj
• Allele Name: targeted mutation 1, Alexandra L Joyner
• Allele ID: MGI:1857164
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	En2^tm1Alj/En2^tm1Alj	either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * CD-1)	MGI:2175853
hm2	En2^tm1Alj/En2^tm1Alj	involves: 129S2/SvPas * C57BL/6	MGI:3719798
hm3	En2^tm1Alj/En2^tm1Alj	involves: 129/Sv * 129S2/SvPas	MGI:3720018
ht4	En2^tm1Alj/En2^+	either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * CD-1)	MGI:2175854
cn5	En1^tm1Alj/En1^tm8.1Alj En2^tm1Alj/En2^tm7.1Alj Gt(ROSA)26Sor^tm1(cre/ERT2)Alj/Gt(ROSA)26Sor^+	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:4421427
cn6	En2^tm1Alj/En2^tm6Alj Gt(ROSA)26Sor^tm1(cre/ERT2)Alj/Gt(ROSA)26Sor^+	involves: 129S2/SvPas * 129S6/SvEvTac * Swiss Webster	MGI:4421426
cn7	En1^tm1Alj/En1^tm8.1Alj En2^tm1Alj/En2^tm6Alj Gt(ROSA)26Sor^tm1(cre/ERT2)Alj/Gt(ROSA)26Sor^+	involves: 129S2/SvPas * 129S6/SvEvTac * Swiss Webster	MGI:4421433
cx8	En1^tm1Alj/En1^tm8.1Alj En2^tm1Alj/En2^tm7.1Alj	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:4421431
cx9	En1^tm1Alj/En1^+ En2^tm1Alj/En2^tm1Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3718800
cx10	En1^tm1Alj/En1^tm1Alj En2^tm1Alj/En2^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3718799
cx11	En1^tm1Gld/En1^tm1Gld En2^tm1Alj/En2^tm1Alj	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839947
cx12	En1^tm1Gld/En1^tm1Gld En2^tm1Alj/En2^+	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839948
cx13	En1^tm1Gld/En1^+ En2^tm1Alj/En2^tm1Alj	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839946

Genotype
MGI:2175853

hm1

• Allelic Composition: En2^tm1Alj/En2^tm1Alj
• Genetic Background: either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * CD-1)

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

nervous system

abnormal cerebellum development ( J:67524 )

abnormal cerebellar foliation ( J:31921 , J:67524 )

• abnormal folding of the paraflocculus (J:31921)

• fused folds in the hemispheres results in 3 rather than 4 lobules (J:31921)

• altered pattern (J:67524)

• reduction of Crus I and Crus II (J:67524)

• reduced paraflocculus (J:67524)

abnormal cerebellum vermis morphology ( J:67524 )

• extended tuber vermis or pyramis

abnormal cerebellum posterior vermis morphology ( J:31921 )

• abnormal folding of the posterior vermis

small cerebellum ( J:31921 , J:67524 )

• size reductions and delayed midline fusion observed embryonically (J:31921)

• reduced in size at 8 weeks of age (J:67524)

behavior/neurological

impaired coordination ( J:31921 )

• improvement in performance with initial testing on a rotarod but improvement is less with later testing

abnormal locomotor activation ( J:31921 )

• less habituation observed in locomotor activity tests

digestive/alimentary system

increased defecation amount ( J:31921 )

• observed in open field and bar cross behavior tests

Genotype
MGI:3719798

hm2

• Allelic Composition: En2^tm1Alj/En2^tm1Alj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

behavior/neurological

abnormal spatial learning ( J:114464 )

• deficient performance in a hidden platform test

abnormal grooming behavior ( J:114464 )

decreased grooming behavior ( J:114464 )

• reduced allogrooming among juveniles

increased grooming behavior ( J:114464 )

• increased allogrooming among males rather than aggressive behavior

abnormal motor capabilities/coordination/movement ( J:114464 )

abnormal motor coordination/balance ( J:114464 )

impaired righting response ( J:114464 )

• while falling but not on a flat surface

impaired coordination ( J:114464 )

• poor performance on rotarod tests

abnormal grip strength ( J:114464 )

• deficient

hyperactivity ( J:114464 )

• from age 21-27 days

abnormal social/conspecific interaction behavior ( J:114464 )

decreased aggression towards mice ( J:114464 )

• latency to attack is increased in adult males

abnormal social investigation ( J:114464 )

• significantly reduced social interactions (play) in juveniles

• hypoactivity

• less sniffing

homeostasis/metabolism

increased serotonin level ( J:114464 )

• increased serotonin in the cerebellum

• increased 5-hydroxyindolacetic acid in the cerebellum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:114464

Genotype
MGI:3720018

hm3

• Allelic Composition: En2^tm1Alj/En2^tm1Alj
• Genetic Background: involves: 129/Sv * 129S2/SvPas

nervous system

decreased colliculi size ( J:17203 )

• reduced in size by E15.5-E16.5

abnormal cerebellum morphology ( J:17203 )

abnormal cerebellum development ( J:17203 )

• 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

abnormal cerebellar foliation ( J:17203 )

• altered pattern

• failure of ansoparamedial fissure to form resulting of fusion of crus II with paramedial lobule

• 3 rather than 4 major folds

thin external granule cell layer ( J:17203 )

• external granular layer is decreased in thickness between E15 and 9 days of age

abnormal cerebellar granule layer morphology ( J:17203 )

• delayed formation of inner granular layer

abnormal cerebellum posterior vermis morphology ( J:17203 )

• 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

Genotype
MGI:2175854

ht4

• Allelic Composition: En2^tm1Alj/En2⁺
• Genetic Background: either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * CD-1)

behavior/neurological

abnormal behavior ( J:31921 )

• moderate behavioral impairment

Genotype
MGI:4421427

cn5

• Allelic Composition: En1^tm1Alj/En1^tm8.1Alj; En2^tm1Alj/En2^tm7.1Alj; Gt(ROSA)26Sor^{tm1(cre/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellar foliation ( J:156169 )

abnormal cerebellum hemisphere lobule morphology ( J:156169 )

• when given tamoxifen at E13.5 or E14. the hemisphere phenotype is more severe than in double mutants that do not express Cre

abnormal cerebellum vermis lobule morphology ( J:156169 )

• when given tamoxifen at E13.5 or E14. the vermis phenotype is more severe than in double mutants that do not express Cre

Genotype
MGI:4421426

cn6

• Allelic Composition: En2^tm1Alj/En2^tm6Alj; Gt(ROSA)26Sor^{tm1(cre/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * Swiss Webster

nervous system

abnormal cerebellar foliation ( J:156169 )

• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice

abnormal cerebellum hemisphere lobule morphology ( J:156169 )

• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice

abnormal cerebellum vermis lobule morphology ( J:156169 )

• following tamoxifen administration at E9.5 - E12.5, all or almost all display an abnormal foliation pattern similar to that in En2 null mice

Genotype
MGI:4421433

cn7

• Allelic Composition: En1^tm1Alj/En1^tm8.1Alj; En2^tm1Alj/En2^tm6Alj; Gt(ROSA)26Sor^{tm1(cre/ERT2)Alj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * Swiss Webster

mortality/aging

perinatal lethality, complete penetrance ( J:156169 )

• tamoxifen treatment at E9.5, but not at E10.5, results in death at birth

nervous system

abnormal cerebellar granule cell precursor proliferation ( J:156169 )

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

abnormal midbrain morphology ( J:156169 )

• a major deletion of the midbrain is seen when tamoxifen is given at E9.5, but not when given at E10.5

abnormal cerebellum morphology ( J:156169 )

• 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

abnormal cerebellum development ( J:156169 )

• 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

abnormal cerebellar foliation ( J:156169 )

• 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

abnormal cerebellum external granule cell layer morphology ( J:156169 )

• 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

thin external granule cell layer ( J:156169 )

• when tamoxifen treated at E10.5, at P2 thickness is similar to that at E18.5 and thinner than in the controls.

abnormal cerebellum fissure morphology ( J:156169 )

• 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

abnormal cerebellum vermis morphology ( J:156169 )

decreased anterior vermis size ( J:156169 )

• 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

abnormal cerebellum vermis lobule morphology ( J:156169 )

• 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

abnormal cerebellum posterior vermis morphology ( J:156169 )

• 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

cerebellum vermis hypoplasia ( J:156169 )

• when tamoxifen treated at E10.5, at P2 overall size of each region, and thus total number of cells, is greatly reduced

small cerebellum ( J:156169 )

• when given tamoxifen, at P3 the cerebellum is smaller compared to controls

cellular

abnormal cerebellar granule cell precursor proliferation ( J:156169 )

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

Genotype
MGI:4421431

cx8

• Allelic Composition: En1^tm1Alj/En1^tm8.1Alj; En2^tm1Alj/En2^tm7.1Alj
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellar foliation ( J:156169 )

abnormal cerebellum hemisphere lobule morphology ( J:156169 )

• in the hemispheres, CrusII and Paramedian are only partially separated.

abnormal cerebellum vermis lobule morphology ( J:156169 )

• in adults, only one or two major anterior lobules are present, and lobule VIII is very small and fused with dorsal lobule IX.

Genotype
MGI:3718800

cx9

• Allelic Composition: En1^tm1Alj/En1⁺; En2^tm1Alj/En2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

nervous system

nervous system phenotype ( J:84363 )

N • normal cerebellum

Genotype
MGI:3718799

cx10

• Allelic Composition: En1^tm1Alj/En1^tm1Alj; En2^tm1Alj/En2⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

nervous system

absent cerebellum ( J:84363 )

Genotype
MGI:3839947

cx11

• Allelic Composition: En1^tm1Gld/En1^tm1Gld; En2^tm1Alj/En2^tm1Alj
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster

mortality/aging

perinatal lethality, complete penetrance ( J:115270 )

• die at birth

nervous system

decreased dopaminergic neuron number ( J:115270 )

• decrease in the number of mesencephalic dopaminergic neurons

Genotype
MGI:3839948

cx12

• Allelic Composition: En1^tm1Gld/En1^tm1Gld; En2^tm1Alj/En2⁺
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster

mortality/aging

perinatal lethality, complete penetrance ( J:115270 )

• die at birth

nervous system

decreased dopaminergic neuron number ( J:115270 )

• decrease in the number of mesencephalic dopaminergic neurons

Genotype
MGI:3839946

cx13

• Allelic Composition: En1^tm1Gld/En1⁺; En2^tm1Alj/En2^tm1Alj
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster

nervous system

loss of dopaminergic neurons ( J:115270 )

• 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 neurotransmitter release ( J:115270 )

• 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

abnormal behavior ( J:115270 )

• mice freeze more frequently while swimming compared to En2 null littermate controls

decreased food intake ( J:115270 )

• between 5 and 11 weeks of age, mice consume less food per day compared to En2 null littermate controls

decreased grip strength ( J:115270 )

• 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

decreased locomotor activity ( J:115270 )

• 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/body

slow postnatal weight gain ( J:115270 )

• beginning around 5 to 6 weeks of age

homeostasis/metabolism

decreased dopamine level ( J:115270 )

• in the striatum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:115270