Phenotypes associated with this allele

• Allele Symbol: Tg(SLC18A3-cre)KMisa
• Allele Name: transgene insertion K, Hidemi Misawa
• Allele ID: MGI:2679332
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Chat^tm1Mlt/Chat^tm1Mlt Tg(SLC18A3-cre)KMisa/0	involves: 129 * C57BL/6	MGI:5585431
cn2	Adarb1^tm1.1Skwa/Adarb1^tm1.1Skwa Gria2^tm1.1Phs/Gria2^tm1.1Phs Tg(SLC18A3-cre)KMisa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4843115
cn3	Adarb1^tm1.1Skwa/Adarb1^tm1.1Skwa Tg(SLC18A3-cre)KMisa/0	involves: C57BL/6	MGI:4843114
cn4	Psmc4^tm1.1Ryot/Psmc4^tm1.2Ryot Tg(SLC18A3-cre)KMisa/0	involves: C57BL/6 * C57BL/6N	MGI:5470095
cn5	Atg7^tm1Tchi/Atg7^tm1Tchi Tg(SLC18A3-cre)KMisa/0	involves: C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj	MGI:5470096

Genotype
MGI:5585431

cn1

• Allelic Composition: Chat^tm1Mlt/Chat^tm1Mlt; Tg(SLC18A3-cre)KMisa/0
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

premature death ( J:212048 )

• shorter life span than control animals from 5 months of age

limbs/digits/tail

abnormal gastrocnemius morphology ( J:212048 )

• fibrosis accumulation at 4 months of age

abnormal soleus morphology ( J:212048 )

• fibrosis accumulation at 4 months of age

abnormal tail morphology ( J:212048 )

• tail distortion

skeleton

kyphosis ( J:212048 )

• spinal curve at the level of the thoracic vertebrae

behavior/neurological

abnormal habituation to a new environment ( J:212048 )

tremors ( J:212048 )

tail dragging ( J:212048 )

• in half the animals older than 1 year

abnormal gait ( J:212048 )

• abnormal walk posture (waddling gait)

decreased vertical activity ( J:212048 )

• rearing is severely affected in 6 to 18 months old animals

decreased locomotor activity ( J:212048 )

• spontaneous locomotor activities decreased in 6 to 18 months old animals

nervous system

nervous system phenotype ( J:212048 )

N • normal motor neuron survival in 3 months old animals

growth/size/body

decreased body weight ( J:212048 )

• significantly decreased from 11 months for females and from 4 months of age for males

digestive/alimentary system

rectal prolapse ( J:212048 )

• in half the animals older than 1 year

vision/eye

corneal opacity ( J:212048 )

• in half the animals older than 1 year

muscle

abnormal muscle morphology ( J:212048 )

• decreased proportion of type-I myofibers

abnormal gastrocnemius morphology ( J:212048 )

• fibrosis accumulation at 4 months of age

abnormal soleus morphology ( J:212048 )

• fibrosis accumulation at 4 months of age

skeletal muscle fibrosis ( J:212048 )

• in soleus and gastrocnemius muscle at 4 months of age

skeletal muscle endomysial fibrosis ( J:212048 )

• with incidence and severity worsened with aging

muscular atrophy ( J:212048 )

• progressive muscle fiber atrophy in diaphragm, intercostal, paravertebral, and limb muscles at 17 months of age

muscle weakness ( J:212048 )

• significant decreased time spent on inverted grid test and decreased ability to hold grids of varying weights in 6 to 18 months old animals

Genotype
MGI:4843115

cn2

• Allelic Composition: Adarb1^tm1.1Skwa/Adarb1^tm1.1Skwa; Gria2^tm1.1Phs/Gria2^tm1.1Phs; Tg(SLC18A3-cre)KMisa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:164294 )

N • mice exhibit normal motor function until 6 months of age

nervous system

nervous system phenotype ( J:164294 )

N • motor neuron death observed in Adarb1^tm1.1Skwa/Adarb1^tm1.1Skwa Tg(SLC18A3-cre)KMisa mice is prevented

Genotype
MGI:4843114

cn3

• Allelic Composition: Adarb1^tm1.1Skwa/Adarb1^tm1.1Skwa; Tg(SLC18A3-cre)KMisa/0
• Genetic Background: involves: C57BL/6

mortality/aging

premature death ( J:164294 )

• mice survive 82 weeks compared with 105 weeks for wild-type mice

nervous system

abnormal innervation ( J:164294 )

• ramified axons innervate more than one neuromuscular junction unlike in wild-type mice

motor neuron degeneration ( J:164294 )

• at 2 months

abnormal neuromuscular synapse morphology ( J:164294 )

• ramified axons innervate more than one neuromuscular junction unlike in wild-type mice

abnormal cranial nerve morphology ( J:164294 )

• mice exhibit fewer large neurons in the facial and hypoglossal nerves compared to in wild-type mice

• however, the number of neurons in the oculomotor nerve is normal

abnormal facial nerve morphology ( J:164294 )

• mice exhibit fewer large neurons compared to in wild-type mice

abnormal hypoglossal nerve morphology ( J:164294 )

• mice exhibit fewer large neurons compared to in wild-type mice

abnormal ventral spinal root morphology ( J:164294 )

• the number of myelinated axons in the ventral roots is decreased compared to in wild-type mice

decreased spinal cord ventral horn cell number ( J:164294 )

• between 1 and 2 months of age and slowly decreasing beyond 1 year of age

behavior/neurological

behavior/neurological phenotype ( J:164294 )

N • mice exhibit normal withdrawal response to noxious stimuli

impaired coordination ( J:164294 )

• rotarod performance decreases from 5 weeks through 5 to 6 months of age and further after 18 months in comparison with wild-type mice

decreased grip strength ( J:164294 )

abnormal posture ( J:164294 )

• of the hind limb and tail

abnormal limb posture ( J:164294 )

• of the hind limb

decreased locomotor activity ( J:164294 )

• mice are hypokinetic unlike wild-type mice

muscle

abnormal skeletal muscle fiber morphology ( J:164294 )

• skeletal muscles exhibit pyknotic nuclear clumps unlike in wild-type mice

skeletal muscle fiber atrophy ( J:164294 )

centrally nucleated skeletal muscle fibers ( J:164294 )

growth/size/body

decreased body weight ( J:164294 )

• slightly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis		DOID:332	OMIM:PS105400	J:164294

Genotype
MGI:5470095

cn4

• Allelic Composition: Psmc4^tm1.1Ryot/Psmc4^tm1.2Ryot; Tg(SLC18A3-cre)KMisa/0
• Genetic Background: involves: C57BL/6 * C57BL/6N

Limb clasping and severe kyphosis in Psmc4^tm1.1Ryot/Psmc4^tm1.2Ryot Tg(SLC18A3-cre)KMisa/0 mice

mortality/aging

mortality/aging ( J:193770 )

N • mice exhibit normal survival until at least 48 weeks of age

nervous system

microgliosis ( J:193770 )

• at 12 weeks with few at 40 weeks of age

astrocytosis ( J:193770 )

• as early as 6 weeks of age and persisting until 40 weeks of age

abnormal motor neuron morphology ( J:193770 )

• chromatolytic neurons and basophilic inclusions with eosinophilic cytoplasm at 12 weeks of age

decreased motor neuron number ( J:193770 )

• from 6 weeks of age

motor neuron degeneration ( J:193770 )

• loss of motor neurons with cytoplasmic Tardbp/TDP-43

behavior/neurological

limb grasping ( J:193770 )

• 35 week old mice show abnormal limb clasping reflex during tail hanging

tremors ( J:193770 )

• disturbed and tremulous hindlimb movement with tail suspension

impaired coordination ( J:193770 )

• progressive deterioration of motor function after 26 weeks of age

decreased grip strength ( J:193770 )

skeleton

kyphosis ( J:193770 )

• severe at advanced stage indicating weakness of paraspinal muscles

growth/size/body

decreased body weight ( J:193770 )

hematopoietic system

microgliosis ( J:193770 )

• at 12 weeks with few at 40 weeks of age

immune system

microgliosis ( J:193770 )

• at 12 weeks with few at 40 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis		DOID:332	OMIM:PS105400	J:193770

Genotype
MGI:5470096

cn5

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Tg(SLC18A3-cre)KMisa/0
• Genetic Background: involves: C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj

behavior/neurological

behavior/neurological phenotype ( J:193770 )

N • mice exhibit normal motor function

nervous system

abnormal motor neuron morphology ( J:193770 )

• with amorphous structures and large inclusions at 2 years of age

• however, there is no loss of motor neurons