Phenotypes associated with this allele

• Allele Symbol: En1^tm1Gld
• Allele Name: targeted mutation 1, Martyn Goulding
• Allele ID: MGI:2137030
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	En1^tm1Gld/En1^tm1Gld	involves: 129S/SvEv	MGI:3839919
hm2	En1^tm1Gld/En1^tm1Gld	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839949
hm3	En1^tm1Gld/En1^tm1Gld	involves: 129S/SvEv * C57BL/6	MGI:3839923
cx4	En1^tm1Gld/En1^+ Ntn1^Gt(ST629)Byg/Ntn1^Gt(ST629)Byg	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6	MGI:3839924
cx5	En1^tm1Gld/En1^tm1Gld Tg(Wnt1-En1)1Amc/0	involves: 129S/SvEv	MGI:3839920
cx6	En1^tm1Gld/En1^+ En2^tm1Alj/En2^tm1Alj	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839946
cx7	En1^tm1Gld/En1^tm1Gld En2^tm1Alj/En2^tm1Alj	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839947
cx8	En1^tm1Gld/En1^tm1Gld En2^tm1Alj/En2^+	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * Swiss Webster	MGI:3839948

Genotype
MGI:3839919

hm1

• Allelic Composition: En1^tm1Gld/En1^tm1Gld
• Genetic Background: involves: 129S/SvEv

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

nervous system

abnormal CNS synaptic transmission ( J:106437 )

• spinal cords show a 3- to 4-fold slowing of the locomotor step cycle and lengthening of the burst duration

Genotype
MGI:3839949

hm2

• Allelic Composition: En1^tm1Gld/En1^tm1Gld
• 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:3839923

hm3

• Allelic Composition: En1^tm1Gld/En1^tm1Gld
• Genetic Background: involves: 129S/SvEv * C57BL/6

nervous system

abnormal neuron differentiation ( J:52637 )

• at E10.5 axons from En1 expressing neurons form bundles of 3 or more axons within the ventrolateral funiculus unlike in controls where axons do not fasciculate with each other

• at E12 axons from En1 expressing neurons form bundles of 10 or more axons within the ventrolateral funiculus unlike in controls

abnormal axon guidance ( J:52637 )

• at E10.5 axons from En1 expressing neurons often turn dorsally after entering the ventrolateral funiculus rather than turning rostrally

• at E12 axons from En1 expressing neurons display disorganized trajectories

• at E12.5 axons from En1 expressing neurons are absent from the ventromedial regions of the ventrolateral funiculus with few if any axons adjacent to the medial most motor neurons

decreased midbrain size ( J:52637 )

• truncation of the midbrain is seen at E12

abnormal innervation ( J:52637 )

• fewer axons from En1 expressing neurons are present in the medial half of the medial motor column and more axons are present in the lateral half

limbs/digits/tail

abnormal limb morphology ( J:52637 )

• limb defects are seen at E12

cellular

abnormal neuron differentiation ( J:52637 )

• at E10.5 axons from En1 expressing neurons form bundles of 3 or more axons within the ventrolateral funiculus unlike in controls where axons do not fasciculate with each other

• at E12 axons from En1 expressing neurons form bundles of 10 or more axons within the ventrolateral funiculus unlike in controls

abnormal axon guidance ( J:52637 )

• at E10.5 axons from En1 expressing neurons often turn dorsally after entering the ventrolateral funiculus rather than turning rostrally

• at E12 axons from En1 expressing neurons display disorganized trajectories

• at E12.5 axons from En1 expressing neurons are absent from the ventromedial regions of the ventrolateral funiculus with few if any axons adjacent to the medial most motor neurons

Genotype
MGI:3839924

cx4

• 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:3839920

cx5

• Allelic Composition: En1^tm1Gld/En1^tm1Gld; Tg(Wnt1-En1)1Amc/0
• Genetic Background: involves: 129S/SvEv

behavior/neurological

impaired coordination ( J:106437 )

• impaired ability to walk and maintain balance at higher rotarod speeds

• while performance improves with practice mice never match the performance of wild-type controls

Genotype
MGI:3839946

cx6

• 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

Genotype
MGI:3839947

cx7

• 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

cx8

• 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