Mouse Genome Informatics
cx1
    Gt(ROSA)26Sortm1.1(CAG-PLS3,-GFP)Bwir/Gt(ROSA)26Sor+
Smn1tm1Hung/Smn1+
Tg(SMN2)2Hung/0

B6N.Cg-Gt(ROSA)26Sortm1.1(CAG-PLS3,-GFP)Bwir Smn1tm1Hung Tg(SMN2)2Hung
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• increased motor neuron size compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• at P4 and P8, endplate size is increased compared to in Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• at P1 and P4, endplates exhibit an increase in axon input compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice


Mouse Genome Informatics
cx2
    Gt(ROSA)26Sortm1.1(CAG-PLS3,-GFP)Bwir/Gt(ROSA)26Sor+
Smn1tm1Hung/Smn1tm1Hung
Tg(SMN2)2Hung/0

B6N.Cg-Gt(ROSA)26Sortm1.1(CAG-PLS3,-GFP)Bwir Smn1tm1Hung Tg(SMN2)2Hung
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice

nervous system
• increased motor neuron size with increased proprioceptive nerves compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
• increased proprioceptive nerves in contact with motor neurons compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
• at P4, P8 and P11, endplate size is increased compared to in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
• at P1, P4 and P8, endplates exhibit an increase in axon input compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice

behavior/neurological
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice, mice exhibit impaired motor abilities in tube and righting tests compared with control mice
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice

growth/size
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice

muscle
• compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice


Mouse Genome Informatics
cx3
    Smn1tm1Hung/Smn1tm1Hung
Tg(SMN2)2Hung/0

B6N.Cg-Smn1tm1Hung Tg(SMN2)2Hung
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice exhibit reduced survival compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• Background Sensitivity: mice on a C57BL/6N background exhibit increased survival compared with mice on an FVB/N background but not as much as on a mixed background

nervous system
• decreased motor neuron size with decreased proprioceptive nerves compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• decreased proprioceptive nerves in contact with motor neurons compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• mice exhibit reduced axon input and endplate side compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice

behavior/neurological
• mice exhibit impaired motor abilities in tube and righting tests compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice

muscle
• compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice

growth/size
• mice on a C57BL/6N background are smaller than mice on an FVB/N or mixed background
• compared with Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice


Mouse Genome Informatics
cx4
    Smn1tm1Hung/Smn1tm1Hung
Tg(SMN2)2Hung/0

FVB.Cg-Smn1tm1Hung Tg(SMN2)2Hung/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: mice on an FVB/N background exhibit decreased survival compared with mice on a C57BL/6N or mixed background

nervous system
• Background Sensitivity: mice on an FVB/N background exhibit smaller endplate size compared with mice on a mixed background

muscle
• Background Sensitivity: mice on an FVB/N background exhibit smaller muscle fiber size compared with mice on a mixed background


Mouse Genome Informatics
cx5
    Gt(ROSA)26Sortm1.1(CAG-PLS3,-GFP)Bwir/Gt(ROSA)26Sor+
Smn1tm1Hung/Smn1tm1Hung
Tg(SMN2)2Hung/0

involves: 129P2/OlaHsd * 129S4/SvJae * BALB/cJ * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: unlike mice on a C57BL/6N background, mice on a mixed background exhibit premature death with a modest increased in mean survival compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice

nervous system
N
• unlike in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit restored synaptic vesicle area with an increase in the synaptic vesicle to endplate area ratio at P14, active zones and endplate potential electrophysiology (J:193844)
• mice exhibit an partial restoration of readily releasable pool and quantal content compared with Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung

digestive/alimentary system
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, small intestine mucosal epithelial cells exhibit intracytoplasmatic vacuoles at the tips of the villi and lacteals are occasionally dilated
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria

respiratory system
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces

behavior/neurological
• Background Sensitivity: mice unlike mice on a C57BL/6N background, mice exhibit impaired motor abilities in tube and righting tests that is not as severe as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung mice
• Background Sensitivity: mice unlike mice on a C57BL/6N background, mice on a mixed background exhibit impaired righting that is not as severe as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung

cardiovascular system
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung, mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung
• as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung

growth/size
• Background Sensitivity: mice unlike mice on a C57BL/6N background, mice on a mixed background exhibit decreased body weight that is not as severe as in Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung


Mouse Genome Informatics
cx6
    Smn1tm1Hung/Smn1tm1Hung
Tg(SMN2)2Hung/0

involves: 129P2/OlaHsd * C57BL/6N * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: mice on a mixed background exhibit increased survival compared with mice on a C57BL/6N or FVB/N background

nervous system
• Background Sensitivity: mice on a mixed background exhibit increased endplate size compared with mice on an FVB/N background
• at P4 and P14, the area of nerve terminals occupied by synaptic vesicle area is decreased compared to in Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• at P14, the number of active zones is reduced compared to in Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice
• mice exhibit an increase rise and decay time compared to in Smn1tm1Hung/Smn1+ Tg(SMN2)2Hung mice

digestive/alimentary system
• small intestine mucosal epithelial cells exhibit intracytoplasmatic vacuoles at the tips of the villi and lacteals are occasionally dilated
• mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
• mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
• the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria

respiratory system
• mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12
• lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
• lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces
• lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces

cardiovascular system
• mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12

muscle
• Background Sensitivity: mice on a mixed background exhibit larger muscle fiber size than in mice on an FVB/N background


Mouse Genome Informatics
cx7
    Smn1tm1Hung/Smn1tm1Hung
Tg(SMN2)2Hung/Tg(SMN2)2Hung

involves: 129P2/OlaHsd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice with the most severe phenotype (type 1) die before P10
• mice with an intermediate phenotype (type 2) die at approximately 2-4 weeks
• mice with a mild phenotype (type 3) live a normal lifespan
• mice with an intermediate phenotype (type 2) die at approximately 2-4 weeks

nervous system
• presence of glial bundles observed in anterior spinal root of type 1 mice
• selective loss of thick myelinated fibers observed in anterior spinal root of type 1 mice
• loss of large motor neurons in anterior horns of spinal cord with appearance of empty cell beds
• phenotype is not observed in type 3 mice
• exhibited in motor neurons of anterior horn of type 1 mice
• exhibited in anterior spinal roots
• phenotype is not observed in type 3 mice

muscle
• decreased diameter of muscle fibers in tail
• atrophic fibers associated with hypertrophic type 1 fibers in type 1 mice
• fewer muscle fibers in trunk and limb muscles
• atrophy of muscle bundles in tail, trunk and limb muscles

limbs/digits/tail
• decreased diameter of muscle fibers, atrophy of muscle bundles, group atrophy and subcutaneous edema
• edema is more severe in type 3 than in type 2 mice and rare in type 1 mice
• exhibited by mice with the type 3 phenotype
• 50% of type 1 and 2 mice develop chronic necrosis from the tip of the tail to the root
• exhibited by mice with the type 3 phenotype

homeostasis/metabolism
• subcutaneous edema of tail, most severe in type 3 mice and rare in type 1
• subcutaneous edema of hindlimbs

behavior/neurological
• exhibited in some type 2 mice

growth/size
• exhibited by all three phenotypes, decrease is proportionate to severity of symptoms

integument
• type 1 mice do not develop fur

Mouse Models of Human Disease
OMIM IDRef(s)
Spinal Muscular Atrophy, Type I; SMA1 253300 J:59313