Phenotypes associated with this allele

• Allele Symbol: En1⁺
• Allele Name: wild type
• Allele ID: MGI:1857748
• Summary: 42 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	En1^tm1(Otx2)Wrst/En1^+	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:2175846
ht2	En1^tm1.1(Wnt1)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3047087
ht3	En1^tm1(Wnt1)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3047083
ht4	En1^tm1(Otx2)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1	MGI:3717686
ht5	En1^tm2Alj/En1^+	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3789309
ht6	En1^tm1(PDGFB)Nist/En1^+	involves: 129/Sv * C57BL/6	MGI:3050208
cn7	En1^tm2(cre)Wrst/En1^+ Mfn2^tm1Dcc/Mfn2^tm3Dcc	involves: 129 * 129S4/SvJaeSor * Black Swiss	MGI:3779095
cn8	Dnm1l^tm1.1Hise/Dnm1l^tm1.2Hise En1^tm2(cre)Wrst/En1^+	involves: 129 * C57BL/6 * FVB/N * SJL	MGI:4366518
cn9	Wnt1^tm1.1Mze/Wnt1^tm1.1Mze Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ En1^tm2(cre)Wrst/En1^+	involves: 129 * C57BL/6N	MGI:5495280
cn10	En1^tm2(cre)Gld/En1^+ Gt(ROSA)26Sor^tm1(DTA)Riet/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S1/Sv	MGI:3839921
cn11	Upf2^tm1Btp/Upf2^tm1Btp En1^tm2(cre)Wrst/En1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:6718865
cn12	En1^tm2(cre)Wrst/En1^+ Tor1a^tm1Wtd/Tor1a^tm3.1Wtd	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:5605974
cn13	En1^tm2(cre)Gld/En1^+ Tg(CAG-Bgeo,-AlstR,-EGFP)192Gld/0	involves: 129S1/Sv	MGI:3839922
cn14	Drd2^tm3.1Ebo/Drd2^tm3.1Ebo En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:5431882
cn15	En1^tm7(cre/ESR1)Alj/En1^+ En2^tm2Alj/En2^tm2Alj Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:3789333
cn16	Hbs1l^tm1c(KOMP)Wtsi/Hbs1l^tm1c(KOMP)Wtsi En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6NTac	MGI:6718853
cn17	Gt(ROSA)26Sor^tm7(CAG-mCherry,-EGFP/tetX)Dym/Gt(ROSA)26Sor^+ En1^tm2(cre)Wrst/En1^+ Tg(Fev-flpe)1Dym/0	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ	MGI:4412291
cn18	Gt(ROSA)26Sor^tm7(CAG-mCherry,-EGFP/tetX)Dym/Gt(ROSA)26Sor^+ En1^tm2(cre)Wrst/En1^+ Tg(ACTFLPe)9205Dym/0	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL	MGI:4412289
cn19	En1^tm2(cre)Gld/En1^+ Gli1^tm2Alj/Gli1^tm2Alj Gli2^tm1Alj/Gli2^tm6Alj	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:3665567
cn20	En1^tm2(cre)Gld/En1^+ Gli2^tm1Alj/Gli2^tm6Alj	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:3665558
cn21	En1^tm2(cre)Wrst/En1^+ Tor1a^tm2Wtd/Tor1a^tm3.1Wtd	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6J * SJL	MGI:5605977
cn22	En1^tm2(cre)Wrst/En1^+ Lhx1^tm2.1Bhr/Lhx1^tm2.1Bhr	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:3719688
cn23	En1^tm2(cre)Wrst/En1^+ Lhx1^tm1Tmj/Lhx1^tm2.1Bhr Lhx5^tm1Lmgd/Lhx5^tm1Lmgd	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:3719690
cn24	En1^tm2(cre)Wrst/En1^+ Gata2^tm1Msal/Gata2^tm1Msal	involves: 129S1/Sv * 129X1/SvJ	MGI:4818570
cn25	En1^tm2(cre)Wrst/En1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa	involves: 129S1/Sv * 129X1/SvJ	MGI:3702736
cn26	Slc12a2^tm1.1Jheb/Slc12a2^tm1.1Jheb En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5538345
cn27	En1^tm2(cre)Wrst/En1^+ Fgfr2^tm1Wrst/Fgfr2^tm1Wrst	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3700937
cn28	Ankrd16^tm1.1Slac/Ankrd16^tm1.2Slac En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6197726
cn29	Pelo^tm1Slac/Pelo^tm1Slac En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6718863
cn30	Wnt1^tm1.1Mze/Wnt1^tm1.1Mze En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:5495279
cn31	Atg7^tm1Tchi/Atg7^tm1Tchi En1^tm2(cre)Wrst/En1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6NCrlj * CBA/JNCrlj	MGI:5471363
cn32	En1^tm8.1Alj/En1^+ En2^tm6Alj/En2^+ Gt(ROSA)26Sor^tm1(cre/ERT2)Alj/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * Swiss Webster	MGI:4421432
cn33	Dnm1l^tm1.1Hise/Dnm1l^tm1.1Hise En1^tm2(cre)Wrst/En1^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4366517
cn34	En1^tm2(cre)Wrst/En1^+ Gbx2^tm1.1Mrt/Gbx2^tm1.1Alj	involves: 129/Sv * C57BL/6 * SJL * Swiss Webster	MGI:3790208
cx35	En1^tm1Gld/En1^+ Ntn1^Gt(ST629)Byg/Ntn1^Gt(ST629)Byg	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6	MGI:3839924
cx36	En1^tm1Alj/En1^+ En2^tm1Alj/En2^tm1Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3718800
cx37	En1^tm2Alj/En1^+ En2^tm2Alj/En2^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789303
cx38	En1^tm5(en)Alj/En1^+ En2^tm2Alj/En2^tm2Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789315
cx39	En1^tm2Alj/En1^+ En2^tm2Alj/En2^tm2Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789305
cx40	En1^tm2Alj/En1^+ Tg(Th-EGFP)6-7Okn/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J * OF1	MGI:5604280
cx41	En1^em1Smun/En1^+ Gm29348^em4Smun/Gm29348^+	involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1	MGI:6740444
cx42	En1^tm1Gld/En1^+ En2^tm1Alj/En2^tm1Alj	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839946

Genotype
MGI:2175846

ht1

• Allelic Composition: En1^{tm1(Otx2)Wrst}/En1⁺
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

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

nervous system

abnormal brain morphology ( J:57538 )

abnormal brain commissure morphology ( J:57538 )

• cerebellar commissure ectopically relocated to the surface of the posterior vermis

abnormal corpora quadrigemina morphology ( J:57538 )

increased inferior colliculus size ( J:57538 )

• enlarged and shifted posteriorly

• significantly heavier than controls

increased superior colliculus size ( J:57538 )

• enlarged and shifted posteriorly

abnormal cerebellum morphology ( J:57538 )

• fissures separating the vermis from the lateral hemispheres are missing

abnormal cerebellar lobule formation ( J:57538 )

• lobules are unfused in the midline

• longitudinal rather than transverse fissures are present

absent cerebellar lobules ( J:57538 )

• only posterior lobules (VIII, IX, X) are present

abnormal cerebellum vermis morphology ( J:57538 )

• reduced in size

• not fused in the midline

decreased anterior vermis size ( J:57538 )

• most of the anterior vermis is missing

behavior/neurological

impaired coordination ( J:57538 )

• poor performance in a horizontal thin rod test, improving slightly with practice

• poor performance in a stationary rotarod test, improving slightly with practice

• poor performance in a running rotarod test which does not improve with practice

abnormal locomotor coordination ( J:57538 )

ataxia ( J:57538 )

• gait ataxia

abnormal gait ( J:57538 )

• gait ataxia

Genotype
MGI:3047087

ht2

• Allelic Composition: En1^{tm1.1(Wnt1)Wrst}/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:91004 )

• homozygous mutants die at P0

nervous system

increased inferior colliculus size ( J:91004 )

• the volume of the inferior colliculi is increased

• this increase is more pronounced than in En1^{tm1(Wnt1)Wrst} heterozygotes

Genotype
MGI:3047083

ht3

• Allelic Composition: En1^{tm1(Wnt1)Wrst}/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cellular

abnormal cell cycle ( J:91004 )

• cell cycle length is decreased from 21.1 to 19.9 hours

increased cell proliferation ( J:91004 )

• from E11.5 to E18.5 proliferation of neural progenitors in the inferior colliculi is increased, however no change in tumor formation is seen

nervous system

increased inferior colliculus size ( J:91004 )

• the volume of the inferior colliculi is increased 4.8 fold

• this enlargement can first be detected at E13

abnormal hindbrain morphology ( J:91004 )

• there is a transient increase in the size of the lateral regions of the ventrorostral hindbrain from E10 until E15

abnormal cerebellum morphology ( J:91004 )

• enlargement of the granular cell layer resulting in a slightly undulated appearance of the rostral folia is seen in horizontal sections from adult cerebelli

Genotype
MGI:3717686

ht4

• Allelic Composition: En1^{tm1(Otx2)Wrst}/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1

nervous system

abnormal neuron morphology ( J:88192 )

ectopic dopaminergic neuron ( J:88192 )

• dopaminergic domain expanded posteriorly at E12.5, E15.5, and in adults

abnormal serotonergic neuron morphology ( J:88192 )

• serotonergic neuron domain is shifted caudally and reduced at E12.5, E15.5, and adults

• primarily affects the dorsal raphe

homeostasis/metabolism

increased dopamine level ( J:88192 )

• significantly increased concentrations in the striatum

decreased serotonin level ( J:88192 )

• serotonin concentration in the striatum is significantly reduced

behavior/neurological

increased locomotor activity ( J:88192 )

• enhanced locomotion in adults

Genotype
MGI:3789309

ht5

• Allelic Composition: En1^tm2Alj/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

nervous system

nervous system phenotype ( J:134516 )

N • cerebellum and colliculi have normal morphology at E18.5

Genotype
MGI:3050208

ht6

• Allelic Composition: En1^{tm1(PDGFB)Nist}/En1⁺
• Genetic Background: involves: 129/Sv * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:90898 )

N • no behavioral abnormalities are seen

cardiovascular system

abnormal brain vasculature morphology ( J:90898 )

• the number of small vessels is increased about 40% around the fusion area of the cerebellum

cellular

abnormal cell migration ( J:90898 )

• meningeal cells from the rostral part of the cerebellum appear to migrate into the cerebellar tissue

nervous system

abnormal brain vasculature morphology ( J:90898 )

• the number of small vessels is increased about 40% around the fusion area of the cerebellum

abnormal cerebellum development ( J:90898 )

• at E16 - E17 midline fusion of the cerebellar primordium is abnormal with cells from the posterior cerebellar surface invaginated and establishing centrally located structures

Genotype
MGI:3779095

cn7

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Mfn2^tm1Dcc/Mfn2^tm3Dcc
• Genetic Background: involves: 129 * 129S4/SvJaeSor * Black Swiss

mortality/aging

postnatal lethality, complete penetrance ( J:132329 )

• mutant pups are born at appropriate Mendelian ratio

• after birth, about one third of mutant mice die on postnatal day 1

• all remaining mutant mice die by P17

behavior/neurological

impaired righting response ( J:132329 )

• mice surviving beyond P1 cannot easily regain posture when placed on their backs

impaired limb coordination ( J:132329 )

• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen

growth/size/body

decreased body size ( J:132329 )

• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder

nervous system

abnormal neuron mitochondrial morphology ( J:132329 )

• mitochondria in mutant Purkinje cells in mixed cerebellar cultures tend to cluster together in the cell body and do not enter the dendritic tracts

increased neuron apoptosis ( J:132329 )

• markedly higher levels of apoptosis in mutant cerebella as early as p6 and continuing through the second postnatal week

Purkinje cell degeneration ( J:132329 )

• widespread loss of Purkinje cell bodies py P15 resulting in reduction of the molecular layer

• Purkinje cell loss due to a degenerative process in mixed cerebellar cultures

abnormal Purkinje cell dendrite morphology ( J:132329 )

• reduced growth and deterioration of Purkinje cell dendrite during the second postnatal week

small cerebellum ( J:132329 )

• severe defect in postnatal cerebellar growth

• between P7 and P16, the mutant cerebellum reduces in size

• lobular organization and formation of the three cellular layers is relatively intact

cellular

abnormal neuron mitochondrial morphology ( J:132329 )

• mitochondria in mutant Purkinje cells in mixed cerebellar cultures tend to cluster together in the cell body and do not enter the dendritic tracts

increased neuron apoptosis ( J:132329 )

• markedly higher levels of apoptosis in mutant cerebella as early as p6 and continuing through the second postnatal week

Genotype
MGI:4366518

cn8

• Allelic Composition: Dnm1l^tm1.1Hise/Dnm1l^tm1.2Hise; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB/N * SJL

Defects in cerebellar development in Dnm1l^tm1.1Hise/Dnm1l^tm1.2Hise En1^tm2(cre)Wrst/En1⁺ and Dnm1l^tm1.2Hise/Dnm1l^tm1.2Hise En1^tm2(cre)Wrst/En1⁺ mice

cellular

abnormal Purkinje cell mitochondrial morphology ( J:153835 )

• mitochondria in Purkinje cells are enlarged compared to in wild-type cells

mortality/aging

postnatal lethality, complete penetrance ( J:153835 )

• mice die within 36 hours of birth

nervous system

abnormal cerebellum development ( J:153835 )

• at P0, cerebellum are smooth and exhibit a 60% decreased in size compared to in wild-type mice

reduced cerebellar foliation ( J:153835 )

• at P0, cerebellum lack foliation

• at P0.5, lobule fissures are barely detectable

abnormal cerebellar Purkinje cell layer ( J:153835 )

• Purkinje cells in the cerebellum are decreased in number and form a discontinuous cell layer unlike in wild-type mice

abnormal Purkinje cell mitochondrial morphology ( J:153835 )

• mitochondria in Purkinje cells are enlarged compared to in wild-type cells

decreased Purkinje cell number ( J:153835 )

• in the cerebellum

small cerebellum ( J:153835 )

• at P0, cerebellum are 60% smaller than in wild-type mice due to decreased cell proliferation

behavior/neurological

absent gastric milk in neonates ( J:153835 )

• mice die without milk in their stomach

• however, mice exhibit normal swallowing when manually fed milk

Genotype
MGI:5495280

cn9

• Allelic Composition: Wnt1^tm1.1Mze/Wnt1^tm1.1Mze; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129 * C57BL/6N

nervous system

abnormal rhombomere morphology ( J:194842 )

• rhombomere 1 is diminished with only a small domain adjacent to axonal bundles connected to the trigeminal ganglia

• dorsal rhombomere 1 is severely depleted but the ventral portion is less severely affected

abnormal midbrain morphology ( J:194842 )

• substantial depletion of the En1 lineage derived mesencephalon at E12.5

• dorsal mesencephalon is severely depleted but the ventral portion is less severely affected

abnormal hindbrain morphology ( J:194842 )

• severe truncation of the lateral anterior hindbrain

abnormal innervation ( J:194842 )

• aberrantly patterned whisker fields innervated by serotonergic neurons

decreased neuronal precursor cell number ( J:194842 )

• absence of LMX1a+ progenitors throughout the medial-lateral extent of the ventral mesencephalon and decreased numbers in the ventral diencephalon

decreased neuron number ( J:194842 )

• only a small disorganized cohort of TH+ MbDA neurons remain at E8.5

embryo

abnormal rhombomere morphology ( J:194842 )

• rhombomere 1 is diminished with only a small domain adjacent to axonal bundles connected to the trigeminal ganglia

• dorsal rhombomere 1 is severely depleted but the ventral portion is less severely affected

Genotype
MGI:3839921

cn10

• Allelic Composition: En1^tm2(cre)Gld/En1⁺; Gt(ROSA)26Sor^tm1(DTA)Riet/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

nervous system

abnormal ventral interneuron 1 morphology ( J:106437 )

• decrease in the number of V1 neurons in the spinal cord

abnormal CNS synaptic transmission ( J:106437 )

• significant increase in the length of both step cycle period and motor neuron burst duration during fictive locomotion

Genotype
MGI:6718865

cn11

• Allelic Composition: Upf2^tm1Btp/Upf2^tm1Btp; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

nervous system

increased neuron apoptosis ( J:306384 )

• increased apoptotic cells in the cerebellum in both the ventricular zone and the prospective white matter

increased neuronal precursor proliferation ( J:306384 )

• in the ventricular zone progenitors at E13.5

abnormal cerebellum external granule cell layer morphology ( J:306384 )

• missing at E13.5 and P0

decreased inferior colliculus size ( J:306384 )

• grossly hypoplastic being nearly absent

decreased superior colliculus size ( J:306384 )

• grossly hypoplastic being nearly absent

cerebellum hypoplasia ( J:306384 )

• grossly being nearly absent

loss of GABAergic neurons ( J:306384 )

• at E13.5 in the cerebellum

cellular

increased neuron apoptosis ( J:306384 )

• increased apoptotic cells in the cerebellum in both the ventricular zone and the prospective white matter

increased neuronal precursor proliferation ( J:306384 )

• in the ventricular zone progenitors at E13.5

Genotype
MGI:5605974

cn12

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Tor1a^tm1Wtd/Tor1a^tm3.1Wtd
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

nervous system

gliosis ( J:213785 )

• reactive gliosis is observed in superior cerebellar peduncle and deep cerebellar nuclei

abnormal red nucleus morphology ( J:213785 )

decreased neuron number ( J:213785 )

• decrease in neuron number in red nucleus and deep cerebellar nuclei (DCN) as compared to controls

• neuron loss in DCN is 2 fold higher in this genotype as compared to mice carrying Tor1a^tm2Wtd allele

neurodegeneration ( J:213785 )

• neurodegeneration is observed in midbrain/hindbrain

behavior/neurological

limb grasping ( J:213785 )

• hindlimb and forelimb clasping observed by P15

• forepaw clenching during tail suspension observed by P15

dystonia ( J:213785 )

• twisted truncal postures observed by P15, however, mice do not exhibit spontaneous hind paw twisting

growth/size/body

decreased body weight ( J:213785 )

• mice are weigh less by P28 than littermate controls

muscle

dystonia ( J:213785 )

• twisted truncal postures observed by P15, however, mice do not exhibit spontaneous hind paw twisting

cellular

gliosis ( J:213785 )

• reactive gliosis is observed in superior cerebellar peduncle and deep cerebellar nuclei

Genotype
MGI:3839922

cn13

• Allelic Composition: En1^tm2(cre)Gld/En1⁺; Tg(CAG-Bgeo,-AlstR,-EGFP)192Gld/0
• Genetic Background: involves: 129S1/Sv

nervous system

abnormal CNS synaptic transmission ( J:106437 )

• decrease in V1 neuron excitability in response to current steps and ramps after allatostatin treatment

• application of allatostatin to spinal cords increases the length of the step cycle period

Genotype
MGI:5431882

cn14

• Allelic Composition: Drd2^tm3.1Ebo/Drd2^tm3.1Ebo; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6

behavior/neurological

enhanced behavioral response to xenobiotic ( J:185643 )

• mice fed cocaine exhibit increased locomotion compared with control mice

• mice exhibit enhanced response to nomifensine with greater relative contribution of dopamine transporter activity to peak amplitude compared with control mice

enhanced behavioral response to cocaine ( J:185643 )

• mice treated with cocaine exhibit increased hyperactivity compared with control mice

enhanced behavioral response to anesthetic ( J:185643 )

• mice exhibit increased catalepsy induced by haloperidol compared with control mice

hyperactivity ( J:185643 )

• in an open field

increased vertical activity ( J:185643 )

induced hyperactivity ( J:185643 )

• in mice fed cocaine

nervous system

abnormal nervous system electrophysiology ( J:185643 )

homeostasis/metabolism

abnormal dopamine level ( J:185643 )

• dopamine overflow evoked by a single stimulus in the dorsal striatum (DSt) is decreased compared to in control mice

• mice exhibit lower AMP evoked dopamine release compared with control mice

• dopamine reuptake is increased compared to in control mice

• mice exhibit enhanced response to nomifensine with greater relative contribution of dopamine transporter activity to peak amplitude compared with control mice

• following paired pulse, dopamine overflow is higher than in control mice

• single-pulse evoke dopamine overflow is decreased compared to in control mice

• multiple-pulse evoked dopamine overflow is increased compared to in wild-type mice

• however, quinpirole-treated mice exhibit normal dose-dependent inhibition of dopamine overflow

increased dopamine level ( J:185643 )

• in the nucleus accumbens (NAcc) and cortex

decreased physiological sensitivity to xenobiotic ( J:185643 )

• mice treated with quinpirole exhibit less of a decrease in locomotion compared with control mice

• mice treated with quinpirole in a novel environment fail to exhibit a decrease in locomotion compared with control mice

Genotype
MGI:3789333

cn15

• Allelic Composition: En1^{tm7(cre/ESR1)Alj}/En1⁺; En2^tm2Alj/En2^tm2Alj; Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

nervous system

decreased rhombomere 1 size ( J:134516 )

• when tamoxifen is administered at E10.5, rhombomere 1 (r1) is reduced in size in mutants at E12.5

• anterior r1 cells contribute to more lateral regions of vermis than normal

decreased midbrain size ( J:134516 )

• when tamoxifen is administered at E10.5, mesencephalon is reduced in size at E12.5 relative to normal

• marked cells in posterior mesencephalon do not expand normally

abnormal tectum morphology ( J:134516 )

• when tamoxifen is administered at E10.5, size of marked domain is smaller than wild-type at E16.5

• in adults, marked domain in tectum is greatly reduced compared to wild-type; marked domain is restricted to remaining region of inferior colliculus

abnormal cerebellum morphology ( J:134516 )

• when tamoxifen is administered at E10.5, size of marked cell population is wider in mutants than in controls at E16.5

• in adults, marked domain is broader than normal

abnormal cerebellum vermis morphology ( J:134516 )

• in adults, vermis is reduced in size

embryo

decreased rhombomere 1 size ( J:134516 )

• when tamoxifen is administered at E10.5, rhombomere 1 (r1) is reduced in size in mutants at E12.5

• anterior r1 cells contribute to more lateral regions of vermis than normal

Genotype
MGI:6718853

cn16

• Allelic Composition: Hbs1l^{tm1c(KOMP)Wtsi}/Hbs1l^{tm1c(KOMP)Wtsi}; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6NTac

nervous system

increased neuronal precursor proliferation ( J:306384 )

• more GABAergic precursors are retained between E12.5 and E16.5 due to increased proliferation

abnormal cerebellum morphology ( J:306384 )

• cerebellar defects are not rescued by restoration or complete deletion of n-TRtct5

abnormal cerebellar foliation ( J:306384 )

• delayed at P0 with failure of secondary fissures to form

• however, the trilaminar structure is normal at P21

decreased Purkinje cell number ( J:306384 )

• reduced ventricular zone-derived Lhx1/5+ Purkinje cells between E12.5 and E16.5

small cerebellum ( J:306384 )

• by E13.5

abnormal GABAergic neuron morphology ( J:306384 )

• more GABAergic precursors are retained between E12.5 and E16.5 due to increased proliferation

decreased neuronal precursor cell number ( J:306384 )

• reduced Pax2+ interneuron precursors between E12.5 and E16.5

• reduced granule cell precursors at E13.5 to E16.5

• reduced oligodendroglial progenitors at P5

• however, granule cell precursor proliferation is normal at E16.5 and P5

cellular

increased neuronal precursor proliferation ( J:306384 )

• more GABAergic precursors are retained between E12.5 and E16.5 due to increased proliferation

Genotype
MGI:4412291

cn17

• Allelic Composition: Gt(ROSA)26Sor^{tm7(CAG-mCherry,-EGFP/tetX)Dym}/Gt(ROSA)26Sor⁺; En1^tm2(cre)Wrst/En1⁺; Tg(Fev-flpe)1Dym/0
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

behavior/neurological

behavior/neurological phenotype ( J:154944 )

N • mice exhibit normal contextual fear conditioning and prepulse mediated inhibition of acoustic startle reflex

decreased anxiety-related response ( J:154944 )

nervous system

abnormal axon morphology ( J:154944 )

• 5HT+ axon varicosities are enlarged compared to in wild-type mice

Genotype
MGI:4412289

cn18

• Allelic Composition: Gt(ROSA)26Sor^{tm7(CAG-mCherry,-EGFP/tetX)Dym}/Gt(ROSA)26Sor⁺; En1^tm2(cre)Wrst/En1⁺; Tg(ACTFLPe)9205Dym/0
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

perinatal lethality ( J:154944 )

Genotype
MGI:3665567

cn19

• Allelic Composition: En1^tm2(cre)Gld/En1⁺; Gli1^tm2Alj/Gli1^tm2Alj; Gli2^tm1Alj/Gli2^tm6Alj
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellum morphology ( J:108507 )

• cerebellum has decreased number of fissures compared to conditional Gli2 knockouts

abnormal cerebellum development ( J:108507 )

• only the five cardinal lobes of cerebellum can be discerned; other lobules do not form

abnormal cerebellar foliation ( J:108507 )

• decreased number of lobules (abnormal foliation) is observed

Genotype
MGI:3665558

cn20

• Allelic Composition: En1^tm2(cre)Gld/En1⁺; Gli2^tm1Alj/Gli2^tm6Alj
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

growth/size/body

decreased body size ( J:108507 )

• adults are ~75% of size of wild-type littermates

behavior/neurological

tremors ( J:108507 )

• mice show deficits in motor control such as intention tremors consistent with cerebellar defects

impaired balance ( J:108507 )

• mutants have balance problems

abnormal gait ( J:108507 )

• mice have a wide-based gait

nervous system

nervous system phenotype ( J:108507 )

N • cerebella are similar in volume and thickness to wild-type at E16.5 and do not show the same defects as non-conditional Shh-null animals at that time point

abnormal cerebellar lobule formation ( J:108507 )

• number of lobules in addition to cardinal lobes in vermis and hemispheres is greatly reduced compared to wild-type

abnormal cerebellum external granule cell layer morphology ( J:108507 )

• at birth, EGL of mutants is only one or two cell layers thick compared to 2-4 layers in wild-type; at P5, EGL is only 1 to 4 layers thick compared to 8 to 10 in wild-type

• difference is more apparent at the base of fissures than at crown of lobe

• reduced thickness correlates with delayed onset of foliation and reduced complexity

thin external granule cell layer ( J:108507 )

• at birth, EGL of mutants is only one or two cell layers thick compared to 2-4 layers in wild-type; at P5, EGL is only 1 to 4 layers thick compared to 8 to 10 in wild-type

• difference is more apparent at the base of fissures than at crown of lobe

• reduced thickness correlates with delayed onset of foliation and reduced complexity

abnormal cerebellar Purkinje cell layer ( J:108507 )

• Purkinje cells (PCs) remain multilayered in mutants instead of forming a monolayer as in wild-type

• glial fibers of Bergmann glia are misshapen and disorganized compared to linear, ordered morphology in wild-type

abnormal cerebellar granule layer morphology ( J:108507 )

• internal granule layer (IGL) is thinner compared to wild-type

abnormal cerebellar molecular layer ( J:108507 )

• dendritic arborization of PCs in molecular layer is less branched than normal

abnormal cerebellum vermis morphology ( J:108507 )

• central lobe is divided by a shallow fissure

abnormal cerebellum anterior vermis morphology ( J:108507 )

• fissure dividing anterobasal lobe is absent or shallow in most mutant brains

small cerebellum ( J:108507 )

• adult brains show an extreme decrease in size compared to wild-type while rest of brain appears normal in size

• mediolateral (ML) extent is not as drastically reduced in length compared with anteroposterior (AP) axis

• cerebellum does not increase in size after P8 while in wild-type it grows until P16; only slight growth occurs between P5 and P8; surface area is reduced

Genotype
MGI:5605977

cn21

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Tor1a^tm2Wtd/Tor1a^tm3.1Wtd
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6J * SJL

behavior/neurological

limb grasping ( J:213785 )

• hindlimb and forelimb clasping observed by P15, however, with maturity clasping decreases

• forepaw clenching during tail suspension observed by P15

dystonia ( J:213785 )

• twisted truncal postures observed by P15, however, mice do not exhibit spontaneous twisting of hind paws

impaired coordination ( J:213785 )

• mice exhibit an increase in number of footslip/cross in beam crossing

muscle

dystonia ( J:213785 )

• twisted truncal postures observed by P15, however, mice do not exhibit spontaneous twisting of hind paws

nervous system

gliosis ( J:213785 )

abnormal red nucleus morphology ( J:213785 )

decreased neuron number ( J:213785 )

• decrease in neuron number in red nucleus and deep cerebellar nuclei (DCN) as compared to controls

• neuron loss in DCN is 2 fold less in this genotype as compared to mice carrying Tor1a^tm1Wtd allele

abnormal facial nerve morphology ( J:213785 )

neurodegeneration ( J:213785 )

• neurodegeneration is milder in in this genotype as compared to mice carrying Tor1a^tm1Wtd allele

cellular

gliosis ( J:213785 )

Genotype
MGI:3719688

cn22

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Lhx1^tm2.1Bhr/Lhx1^tm2.1Bhr
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

normal phenotype

no abnormal phenotype detected ( J:123471 )

• viable and fertile

Genotype
MGI:3719690

cn23

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Lhx1^tm1Tmj/Lhx1^tm2.1Bhr; Lhx5^tm1Lmgd/Lhx5^tm1Lmgd
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

nervous system

decreased Purkinje cell number ( J:123471 )

• largely absent at E18.5

absent Purkinje cell layer ( J:123471 )

• layer is absent at E18.5

• however, the external granule cell layer appears normal

small cerebellum ( J:123471 )

• small at E18.5 compared to controls

Genotype
MGI:4818570

cn24

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Gata2^tm1Msal/Gata2^tm1Msal
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

nervous system phenotype ( J:143527 )

N • mice exhibit normal midbrain morphology and neuronal precursor proliferation, survival, patterning, and cell cycle exit

abnormal neuron differentiation ( J:143527 )

• GABAergic precursor cells adopt marker expression similar to precursor cells in glutamatergic regions unlike in wild-type mice

abnormal GABAergic neuron morphology ( J:143527 )

• mice lack GABAergic neuron precursors at the dorsoventral and anteroposterior levels of the midbrain unlike in wild-type mice

• however, GABAergic neurons form in the rhombomere 1 and ventral dopaminergic nuclei

abnormal serotonergic neuron morphology ( J:143527 )

• rhombomere 1 lack serotonergic neurons unlike in wild-type mice

cellular

abnormal neuron differentiation ( J:143527 )

• GABAergic precursor cells adopt marker expression similar to precursor cells in glutamatergic regions unlike in wild-type mice

Genotype
MGI:3702736

cn25

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal midbrain morphology ( J:83004 )

• extensive deletions are seen in the posterior midbrain

• however, no extensive deletions or alterations are seen in the basal plate of the midbrain-hindbrain region and no change in apoptosis is seen in the dorsal midbrain at E9.5

absent inferior colliculus ( J:83004 )

• absence of the inferior colliculus in the posterior midbrain in newborn mice

abnormal locus ceruleus morphology ( J:83004 )

• appears disorganized

abnormal cerebellum morphology ( J:83004 )

• abnormal foliation of the hemispheres

absent cerebellum vermis ( J:83004 )

• absent in newborns and adults

abnormal trochlear nerve morphology ( J:83004 )

• however, in adults the trochlear motoneurons are distinguishable and the oculomotor nerve is normal in both adults and E10.5 embryos

• at E10.5 the dorsal part of the trochlear nerve can not be distinguished

behavior/neurological

impaired coordination ( J:83004 )

• impaired performance in stationary beam and rotarod assays

abnormal posture ( J:83004 )

• adults have a wide stance

abnormal gait ( J:83004 )

Genotype
MGI:5538345

cn26

• Allelic Composition: Slc12a2^tm1.1Jheb/Slc12a2^tm1.1Jheb; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:201156 )

N • no behavioral abnormalities are detected

Genotype
MGI:3700937

cn27

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Fgfr2^tm1Wrst/Fgfr2^tm1Wrst
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

nervous system phenotype ( J:118802 )

N • mutants do not show defects in brain morphology and development (mid/hindbrain patterning, boundary development, neuronal subpopulations, or oligodendrocyte development)

Genotype
MGI:6197726

cn28

• Allelic Composition: Ankrd16^tm1.1Slac/Ankrd16^tm1.2Slac; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

neuron degeneration ( J:262421 )

• of interneurons in the molecular layer and neurons in the granule cell layer with protein aggregates

• of postnatal cortical and hippocampal neurons

Purkinje cell degeneration ( J:262421 )

• with protein aggregates

Genotype
MGI:6718863

cn29

• Allelic Composition: Pelo^tm1Slac/Pelo^tm1Slac; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

increased neuron apoptosis ( J:306384 )

• increased apoptotic cells in the cerebellum in both the ventricular zone and the prospective white matter

increased neuronal precursor proliferation ( J:306384 )

• in the ventricular zone progenitors at E13.5

abnormal cerebellum external granule cell layer morphology ( J:306384 )

• missing at E13.5 and P0

abnormal brain interneuron morphology ( J:306384 )

• decreased Pax2+ interneurons

decreased inferior colliculus size ( J:306384 )

• grossly hypoplastic being nearly absent

decreased superior colliculus size ( J:306384 )

• grossly hypoplastic being nearly absent

decreased Purkinje cell number ( J:306384 )

• reduced Lhx1/5+ Purkinje cells

cerebellum hypoplasia ( J:306384 )

• grossly being nearly absent

loss of GABAergic neurons ( J:306384 )

• at E13.5 in the cerebellum

cellular

increased neuron apoptosis ( J:306384 )

• increased apoptotic cells in the cerebellum in both the ventricular zone and the prospective white matter

increased neuronal precursor proliferation ( J:306384 )

• in the ventricular zone progenitors at E13.5

Genotype
MGI:5495279

cn30

• Allelic Composition: Wnt1^tm1.1Mze/Wnt1^tm1.1Mze; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

nervous system

decreased rhombomere 1 size ( J:194842 )

• severe deletion of rhombomere 1 at E10.5

abnormal midbrain morphology ( J:194842 )

• the ventral mesencephalon is dysmorphic

decreased midbrain size ( J:194842 )

• severe deletion of the putative mesencephalon at E10.5

embryo

decreased rhombomere 1 size ( J:194842 )

• severe deletion of rhombomere 1 at E10.5

Genotype
MGI:5471363

cn31

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6NCrlj * CBA/JNCrlj

mortality/aging

decreased survivor rate ( J:192452 )

• mice show a 76% reduction in survival by 1 year of age

premature death ( J:192452 )

• mice show a 76% reduction in survival by 1 year of age

growth/size/body

weight loss ( J:192452 )

behavior/neurological

tremors ( J:192452 )

• mice exhibit tremulousness

abnormal locomotor behavior ( J:192452 )

• mice show decreased locomotor activity

ataxia ( J:192452 )

abnormal gait ( J:192452 )

• mice exhibit a wide-based and ataxic gait

homeostasis/metabolism

decreased dopamine level ( J:192452 )

• mice exhibit an age dependent decrease in striatal dopamine content in the brain, with a 64.5% reduction by 7-9 months of age compared to controls

nervous system

astrocytosis ( J:192452 )

• a modest increase in reactive astrocytes in the of substantia nigra pars compacta

abnormal brain morphology ( J:192452 )

• while alpha-synuclein inclusions are not seen, accumulation of low-molecular weight alpha-synuclein is seen in the brain

abnormal substantia nigra pars compacta morphology ( J:192452 )

• 60% loss of substantia nigra pars compacta dopamine neurons by 7-9 months of age

abnormal neuron morphology ( J:192452 )

• neuronal inclusions are present in the substantia nigra pars compacta

• inclusions are often perinuclear but are also in the neuropil and are positive for ubiquitin

• neuronal inclusions are present in juveniles but are smaller in size than at older ages

neuron degeneration ( J:192452 )

• 60% loss of substantia nigra pars compacta dopamine neurons by 7-9 months of age

Purkinje cell degeneration ( J:192452 )

cellular

astrocytosis ( J:192452 )

• a modest increase in reactive astrocytes in the of substantia nigra pars compacta

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:192452

Genotype
MGI:4421432

cn32

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

nervous system

abnormal cerebellar foliation ( J:156169 )

abnormal cerebellum fissure morphology ( J:156169 )

• when tamoxifen is given at E13.5 or E14.5 in adult preculminate (between I-II and III) as lobules I-III are fused

abnormal cerebellum posterior vermis morphology ( J:156169 )

• when tamoxifen is given at E10.5, at P14 lobules VI-VII occupied a greater proportion of the vermis than in wild-type

• when tamoxifen is given at E10.5, at P14 lobules VIII-IX occupied a smaller proportion of the vermis than in wild-type

• when tamoxifen is given at E13.5 or E14.5 in adult the vermis has a foliation pattern that was a milder version than that observed in tamoxifen at 10.5 mutants

• when tamoxifen is given at E13.5 or E14.5 in adult posterior region lobule VIII is shifted posterior and fused with dorsal lobule IX.

• when tamoxifen is given at E13.5 or E14.5 in adult lobules I-V and VIII/IX of the vermis were present more laterally than normal tamoxifen at E13.5 or E14.5 in adult lobules I-III were fused into one lobule

Genotype
MGI:4366517

cn33

• Allelic Composition: Dnm1l^tm1.1Hise/Dnm1l^tm1.1Hise; En1^tm2(cre)Wrst/En1⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Defects in cerebellar development in Dnm1l^tm1.1Hise/Dnm1l^tm1.2Hise En1^tm2(cre)Wrst/En1⁺ and Dnm1l^tm1.2Hise/Dnm1l^tm1.2Hise En1^tm2(cre)Wrst/En1⁺ mice

cellular

abnormal Purkinje cell mitochondrial morphology ( J:153835 )

• mitochondria in Purkinje cells are enlarged compared to in wild-type cells

mortality/aging

postnatal lethality, complete penetrance ( J:153835 )

• mice die within 36 hours of birth

nervous system

abnormal cerebellum development ( J:153835 )

• at P0, cerebellum are smooth and exhibit a 60% decreased in size compared to in wild-type mice

reduced cerebellar foliation ( J:153835 )

• at P0, cerebellum lack foliation

• at P0.5, lobule fissures are barely detectable

abnormal cerebellar Purkinje cell layer ( J:153835 )

• Purkinje cells in the cerebellum are decreased in number and form a discontinuous cell layer unlike in wild-type mice

abnormal Purkinje cell mitochondrial morphology ( J:153835 )

• mitochondria in Purkinje cells are enlarged compared to in wild-type cells

decreased Purkinje cell number ( J:153835 )

• in the cerebellum

small cerebellum ( J:153835 )

• at P0, cerebellum are 60% smaller than in wild-type mice due to decreased cell proliferation

behavior/neurological

absent gastric milk in neonates ( J:153835 )

• mice die without milk in their stomach

• however, mice exhibit normal swallowing when manually fed milk

Genotype
MGI:3790208

cn34

• Allelic Composition: En1^tm2(cre)Wrst/En1⁺; Gbx2^tm1.1Mrt/Gbx2^tm1.1Alj
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL * Swiss Webster

mortality/aging

mortality/aging ( J:79431 )

N • more than half of the mice survive past weaning, are fertile and nurture their offspring normally

postnatal lethality, incomplete penetrance ( J:79431 )

• some mutants are found dead prior to weaning age

growth/size/body

decreased body weight ( J:79431 )

• surviving mutants weigh less than wild-type littermates

abnormal postnatal growth ( J:79431 )

• surviving mutants (adults) are smaller than littermates

nervous system

nervous system phenotype ( J:79431 )

N • cerebellar hemisphere development and cytoarchitecture of cerebellum are essentially normal

decreased embryonic neuroepithelium thickness ( J:79431 )

• at E12.5, neuroepithelium of medial cerebellar anlage is thinner than in wild-type with abnormal indents found in the ventricular layer

abnormal cerebellum development ( J:79431 )

• at E10.5, mesencephalon is expanded caudally and alar plate of r1 is significantly reduced

• medial region of cerebellar primordium is reduced in size from E12.5 to 18.5

• increased cell proliferation is observed in indents into ventricular layer, resulting in small cell aggregates in ventricular layer at E14.5; large cell aggregates are observed in medial cerebella of mutants at E18.5

• however, no cell aggregates are seen in cerebella of 8-week old mutants

abnormal cerebellar foliation ( J:79431 )

• foliation pattern is disrupted in adults

• in adult mutants all lobules are reduced in size to varying extents with lobules V and IX less affected

abnormal midbrain development ( J:79431 )

• at E10.5, the mesencephalon is expanded caudally

abnormal midbrain-hindbrain boundary morphology ( J:79431 )

• at E9.5, isthmic constriction dividing the mesencephalon and rhombomere 1 (r1) at dorsal midline is less prominent than in wild-type

increased inferior colliculus size ( J:79431 )

cerebellum vermis hypoplasia ( J:79431 )

decreased embryonic neuroepithelial cell proliferation ( J:79431 )

• proliferation in the medial region of the cerebellum is reduced compared to wild-type

embryo

decreased embryonic neuroepithelium thickness ( J:79431 )

• at E12.5, neuroepithelium of medial cerebellar anlage is thinner than in wild-type with abnormal indents found in the ventricular layer

Genotype
MGI:3839924

cx35

• Allelic Composition: En1^tm1Gld/En1⁺; Ntn1^Gt(ST629)Byg/Ntn1^Gt(ST629)Byg
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6

nervous system

abnormal axon extension ( J:52637 )

• at E11 the majority of En1 expressing neuron ventrally projecting axons are either truncated or turn rostrally before reaching the ventrolateral funiculus

abnormal axon guidance ( J:52637 )

• at E11 the majority of En1 expressing neuron ventrally projecting axons are either truncated or turn rostrally before reaching the ventrolateral funiculus

cellular

abnormal axon extension ( J:52637 )

• at E11 the majority of En1 expressing neuron ventrally projecting axons are either truncated or turn rostrally before reaching the ventrolateral funiculus

abnormal axon guidance ( J:52637 )

• at E11 the majority of En1 expressing neuron ventrally projecting axons are either truncated or turn rostrally before reaching the ventrolateral funiculus

Genotype
MGI:3718800

cx36

• 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:3789303

cx37

• Allelic Composition: En1^tm2Alj/En1⁺; En2^tm2Alj/En2⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellar foliation ( J:134516 )

• delay in cerebellum foliation is observed in adult mice

abnormal cerebellum vermis morphology ( J:134516 )

• in E18.5 mutants, there is a general delay in fissure formation in vermis; less severe than in En2^tm2Alj homozygotes

abnormal cerebellum anterior vermis morphology ( J:134516 )

• vermis displays fused folia, and folia I, II, and III are smaller than normal in adults

abnormal cerebellum posterior vermis morphology ( J:134516 )

• folium VIII is positioned between lobule VII and IX; folium VIII position is shifted posteriorly but less than in En2^tm2Alj homozygotes

small cerebellum ( J:134516 )

• reduced in size

Genotype
MGI:3789315

cx38

• Allelic Composition: En1^tm5(en)Alj/En1⁺; En2^tm2Alj/En2^tm2Alj
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster

nervous system

decreased inferior colliculus size ( J:134516 )

• reduced in size at E18.5

abnormal cerebellum morphology ( J:134516 )

• in posterior hemisphere crusil and paramedian folia are fused; in one embryo, a partial fissure separating crusil and paramedian folia is observed

abnormal cerebellar foliation ( J:134516 )

• foliation defects are milder than in En1^tm2Alj /+, En2^tm2Alj homozygotes; most mutants have foliation pattern similar to hemispheres of En2^tm2Alj homozygotes

abnormal cerebellum posterior vermis morphology ( J:134516 )

• subregion VIII (posterior vermis) is not present at E18.5

small cerebellum ( J:134516 )

• at E18.5, reduced in overall size by one-third relative to controls

Genotype
MGI:3789305

cx39

• Allelic Composition: En1^tm2Alj/En1⁺; En2^tm2Alj/En2^tm2Alj
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster

mortality/aging

mortality/aging ( J:134516 )

N • mutants survive to adulthood

nervous system

abnormal tectum morphology ( J:134516 )

• severely truncated in one mutant and fused with folia I-V remnants

absent inferior colliculus ( J:134516 )

• at E18.5, absent in 1 mutant

decreased inferior colliculus size ( J:134516 )

• at E18.5, structure is absent (1 mutant) or only small amount of tissue is present

• partially truncated in adults

small tectum ( J:134516 )

• at E11.5, truncation of tectum is greater than in En2^tm2Alj homozygotes

abnormal cerebellum morphology ( J:134516 )

• in posterior hemisphere crusil and paramedian folia are fused; in one embryo, a partial fissure separating crusil and paramedian folia is observed at E18.5

• hemispheres are reduced in size compared to En2^tm2Alj adult homozygotes

abnormal cerebellar foliation ( J:134516 )

• delay in cerebellum foliation is more severe than in En2^tm2Alj homozygotes

• there are more foliation defects adults than in En2^tm2Alj adult homozygotes or or En1^tm2Alj / En2^tm2Alj adult double heterozygotes

• in most mutants, the five anterior-most folia (I-V) are replaced by a single fold

abnormal cerebellum anterior vermis morphology ( J:134516 )

• only 1 distinct folium is present in anterior vermis

abnormal cerebellum posterior vermis morphology ( J:134516 )

• substantial deletion of folium VIII is detected in adults

• in some mutants, folium VIII is absent or reduced in size and misaligned with folium IX; in one mutant folia I-V are almost completely absent and fused to profoundly truncated tectum

absent cerebellum vermis ( J:134516 )

• in one mutant at E18.5

absent cerebellum ( J:134516 )

• at E18.5, no cerebellum is observed in some mutants

small cerebellum ( J:134516 )

• reduced in overall size by half at E18.5 in some mutants

• size reduction in adults is greater than in En2^tm2Alj or En1^tm2Alj / En2^tm2Alj adult heterozygotes

• size reduction at E11.5 is greater than in En2^tm2Alj homozygotes

Genotype
MGI:5604280

cx40

• Allelic Composition: En1^tm2Alj/En1⁺; Tg(Th-EGFP)6-7Okn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J * OF1

nervous system

decreased dopaminergic neuron number ( J:214073 )

• nigral tyrosine hydroxylase-positive dopaminergic (TH) neurons are reduced in number by 18% as compared to controls beginning at 16 weeks of age, progressing to 40% at 24 weeks

• numbers of TH+ neurons are similar to controls at 4 weeks

neurodegeneration ( J:214073 )

axon degeneration ( J:214073 )

• progressive degeneration of nigrostriatal axon terminals

axonal dystrophy ( J:214073 )

• enlarged axon terminals contain accumulations of abnormal mitochondria, electron-dense bodies, and abnormal autophagolysosomes

• enlarged axons from the median forebrain bundle appear fragmented and swollen

axonal spheroids ( J:214073 )

• nigrostriatal neurons exhibit spheroidal dystrophic axon terminals beginning at 8 days

• spheroids contain electron dense autophagic vacuoles

abnormal synaptic dopamine release ( J:214073 )

• nigrostriatal terminals in the dorsal striatum of 16 week old mice are deficient in KCl-evoked dopamine release and uptake

homeostasis/metabolism

abnormal autophagy ( J:214073 )

• autophagic protein degradation is reduced in dopaminergic neurons

decreased dopamine level ( J:214073 )

• dopamine levels in the striatum of 4 week old mice are 27% lower than controls and progress to 46% by 24 weeks of age

cellular

abnormal autophagy ( J:214073 )

• autophagic protein degradation is reduced in dopaminergic neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:214073

Genotype
MGI:6740444

cx41

• Allelic Composition: En1^em1Smun/En1⁺; Gm29348^em4Smun/Gm29348⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCrl * CD-1

limbs/digits/tail

abnormal limb morphology ( J:306235 )

• severe double dorsal-limb defects

nervous system

nervous system phenotype ( J:306235 )

N • mice exhibit normal brains

skeleton

skeleton phenotype ( J:306235 )

N • mice exhibit normal sternum and ribs

Genotype
MGI:3839946

cx42

• 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