Phenotypes associated with this allele

• Allele Symbol: En1^tm2Alj
• Allele Name: targeted mutation 2, Alexandra L Joyner
• Allele ID: MGI:1857749
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	En1^tm2Alj/En1^tm2Alj	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3789307
ht2	En1^tm2Alj/En1^+	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3789309
cx3	En1^tm2Alj/En1^tm3(En2)Alj En2^tm2Alj/En2^tm2Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789316
cx4	En1^tm2Alj/En1^tm2Alj En2^tm2Alj/En2^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789302
cx5	En1^tm2Alj/En1^tm2Alj En2^tm2Alj/En2^tm2Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:2171403
cx6	En1^tm2Alj/En1^+ En2^tm2Alj/En2^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789303
cx7	En1^tm2Alj/En1^+ En2^tm2Alj/En2^tm2Alj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Swiss Webster	MGI:3789305
cx8	En1^tm2Alj/En1^+ Tg(Th-EGFP)6-7Okn/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J * OF1	MGI:5604280

Genotype
MGI:3789307

hm1

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

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

nervous system

decreased rhombomere 1 size ( J:134516 )

• amount of rhombomere 1 tissue is reduced in mutants

decreased midbrain size ( J:134516 )

• amount of tissue is reduced in mutants

absent inferior colliculus ( J:134516 )

• structure does not form

decreased superior colliculus size ( J:134516 )

• reduced in size; in some animals only small amount of tissue forms

abnormal cerebellum morphology ( J:134516 )

• some lateral tissue is present at E18.5

abnormal cerebellum posterior vermis morphology ( J:134516 )

embryo

decreased rhombomere 1 size ( J:134516 )

• amount of rhombomere 1 tissue is reduced in mutants

Genotype
MGI:3789309

ht2

• 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:3789316

cx3

• Allelic Composition: En1^tm2Alj/En1^tm3(En2)Alj; 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:3789302

cx4

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

mortality/aging

perinatal lethality, complete penetrance ( J:134516 )

• no mutants are detected after birth

nervous system

absent inferior colliculus ( J:134516 )

• absent at E18.5

absent superior colliculus ( J:134516 )

• absent at E18.5

absent colliculi ( J:134516 )

absent tectum ( J:134516 )

absent cerebellum ( J:134516 )

• at E18.5, no cerebellum is observed

Genotype
MGI:2171403

cx5

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

nervous system

absent rhombomere 1 ( J:66592 )

• most or all of r1 deleted by E9.5

decreased rhombomere 1 size ( J:66592 )

• most or all of r1 deleted by E9.5

abnormal midbrain-hindbrain boundary development ( J:66592 )

• development normal through early somite stage but abnormal by 10-12 somite stage

absent midbrain-hindbrain boundary ( J:66592 )

• general deletion of the mesencephalon/anterior metencephalon region at E9.5

absent inferior colliculus ( J:134516 )

• absent at E18.5

absent superior colliculus ( J:134516 )

• absent at E18.5

absent colliculi ( J:134516 )

absent tectum ( J:134516 )

absent midbrain ( J:66592 )

• mostly, if not entirely, deleted at E9.5

small cerebellum ( J:134516 )

• reduced in overall size by one-third at E18.5

embryo

absent rhombomere 1 ( J:66592 )

• most or all of r1 deleted by E9.5

decreased rhombomere 1 size ( J:66592 )

• most or all of r1 deleted by E9.5

Genotype
MGI:3789303

cx6

• 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:3789305

cx7

• 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

cx8

• 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