Phenotypes associated with this allele

• Allele Symbol: Smn1^tm1Cdid
• Allele Name: targeted mutation 1, Christine DiDonato
• Allele ID: MGI:4836030
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smn1^tm1Cdid/Smn1^tm1Cdid	involves: 129 * C57BL/6	MGI:5290107
cn2	Mnx1^tm4(cre)Tmj/Mnx1^+ Smn1^tm1Cdid/Smn1^tm1Cdid Grm7^Tg(SMN2)89Ahmb/Grm7^+	involves: 129 * 129S1/Sv * C57BL/6 * FVB	MGI:5318858
cx3	Smn1^tm1Cdid/Smn1^tm1Cdid Grm7^Tg(SMN2)89Ahmb/Grm7^+	involves: 129 * C57BL/6 * FVB	MGI:5318856
cx4	Smn1^tm1Cdid/Smn1^tm1.1Cdid Grm7^Tg(SMN2)89Ahmb/Grm7^+	involves: 129 * C57BL/6 * FVB	MGI:5318857

Genotype
MGI:5290107

hm1

• Allelic Composition: Smn1^tm1Cdid/Smn1^tm1Cdid
• Genetic Background: involves: 129 * C57BL/6

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

embryo

embryonic growth arrest ( J:176267 )

• embryos are developmentally delayed at E9.5

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:176267 )

• die between E9.5 and E12.5

Genotype
MGI:5318858

cn2

• Allelic Composition: Mnx1^tm4(cre)Tmj/Mnx1⁺; Smn1^tm1Cdid/Smn1^tm1Cdid; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: involves: 129 * 129S1/Sv * C57BL/6 * FVB

mortality/aging

postnatal lethality, complete penetrance ( J:183080 )

• median survival of 12 days

nervous system

nervous system phenotype ( J:183080 )

N • neuromuscular junctions are similar to controls in the intercostal and triangularis sterni muscles

abnormal innervation ( J:183080 )

• decrease in cardiac autonomic innervation

decreased motor neuron number ( J:183080 )

• in L3-L5 spinal cord sections but not in the cervical or thoracic regions

cardiovascular system

decreased heart rate ( J:183080 )

• by P9

irregular heartbeat ( J:183080 )

• end-stage mice display skipped or dropped beats

prolonged PR interval ( J:183080 )

• at P9-P11

prolonged QT interval ( J:183080 )

• at P9-P11

behavior/neurological

behavior/neurological phenotype ( J:183080 )

N • ambulatory throughout life

lethargy ( J:183080 )

• early in life

• outgrow this passive behavior after P6

abnormal motor coordination/balance ( J:183080 )

• lateral instability of the hind limbs

abnormal righting response ( J:183080 )

• significantly improved righting response

growth/size/body

decreased body weight ( J:183080 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:183080

Genotype
MGI:5318856

cx3

• Allelic Composition: Smn1^tm1Cdid/Smn1^tm1Cdid; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB

mortality/aging

postnatal lethality, complete penetrance ( J:183080 )

• median survival is 7 days

nervous system

abnormal innervation pattern to muscle ( J:183080 )

• significant decrease in the number of fully innervated motor endplates and increase in the number of partially innervated and denervated endplates in the intercostal muscle

• however, innervation of the endplates in the triangularis sterni muscle is similar to controls

abnormal neuromuscular synapse morphology ( J:183080 )

• increase in intercostal muscle homogeneous motor endplates and decrease in the number of endplates containing secondary structure

• however, endplates in the triangularis sterni muscle are similar to controls

• decrease in the number of glutamatergic excitatory synapses at P5 in the L2-L5 region of the spinal cord

abnormal spinal cord morphology ( J:183080 )

• decrease in the number of glutamatergic excitatory synapses at P5 in the L2-L5 region of the spinal cord

• significant loss in average MNs per ventral horn is seen in cervical, thoracic, and lumbar spinal cords

decreased motor neuron number ( J:183080 )

• significant loss in average MNs per ventral horn is seen in cervical, thoracic, and lumbar spinal cords

motor neuron degeneration ( J:183080 )

• signs of neurodegeneration in the intercostal muscle

decreased single cell response threshold ( J:183080 )

• threshold voltage in motor neurons is significantly lower and amplitude of the persistent inward current is significantly larger indicating increased excitability in cultured motor neurons

• high frequency of postsynaptic potentials in cultured motor neurons

cardiovascular system

decreased heart rate ( J:183080 )

• by P3 and declines over time

prolonged PR interval ( J:183080 )

• at P3-P7

prolonged QRS complex duration ( J:183080 )

• at P3-P7

prolonged QT interval ( J:183080 )

• at P3-P7

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:183080 )

• decreased motor function

impaired righting response ( J:183080 )

• never develop the ability to right when placed on the back

paralysis ( J:183080 )

• near complete paralysis by P5

growth/size/body

decreased body weight ( J:183080 )

• at P2 or later

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:183080

Genotype
MGI:5318857

cx4

• Allelic Composition: Smn1^tm1Cdid/Smn1^tm1.1Cdid; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB

normal phenotype

no abnormal phenotype detected ( J:183080 )

• viable and indistinguishable from control littermates