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| Nomenclature |
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Symbol:
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Tg(SMN1*A2G)2023Ahmb
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Name:
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transgene insertion 2023, Arthur H M Burghes
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MGI ID: |
MGI:2448969 |
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Synonyms: |
SMN A2G |
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Transgene:
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Tg(SMN1*A2G)2023Ahmb
Location:
unknown
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Transgene
origin |
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Transgene
description |
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Transgene
Type: | |
Transgenic (random, expressed) |
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Mutation: | |
Insertion |
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Mutation details: A 4.9 kb construct carrying a human SMN1 cDNA with an A2G missense mutation in exon 1, under control of the human SMN promoter, was used for the transgene. Line 2023 carries 11 copies of the transgene. (J:81238)
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Phenotypes
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View phenotypes for all genotypes (concatenated display).
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Disease models
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| Find Mice (IMSR) |
Mouse strains and cell lines available from the
International Mouse Strain Resource
(IMSR)
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Notes |
Hemizygous mice that are also hemizygous for Tg(SMN2)89Ahmb and homozygous for Smn1tm1Msd exhibit symptoms and neuropathology similar to patients afflicted with type III (mild) proximal spinal muscular atrophy (SMA). Triple mutants are 20%-40% smaller than unaffected mice. At 3 weeks of age they become less active and show signs of muscle weakness. The mice have a shortened lifespan (less than a year) near the end of which they exhibit reduced movement, diminished grooming, shallow breathing and considerable weight loss. Immunohistochemical analysis of spinal cord tissue from one month-old animals indicates the presence of cytoplasmic SMN protein and intranuclear aggregates (gems) of the SMN protein. Histological analysis of muscle tissue (gastrocnemius, quadriceps, and intercostals muscles) reveals numerous angulated and atrophic fibers. This trait is more pronounced in the gastrocnemius muscle tissue. Reduced numbers of motor neurons are observed in lumbar spinal cord (29% fewer) and facial nucleus (~19% fewer) tissues derived from 3.5-month-old triple mutant mice. Normal numbers of motor neurons are found in 5 day-old mice, indicating that motor neuron loss is a later event in SMA. Electromyograph (EMG) recordings from 4-6 month old triple mutants provide a clear indication of denervation. Associated compensatory axon sprouting is observed. Triple mutants homozygous for the SMN1 A2G transgene display a much milder phenotype, live longer and breed well. Hemizygotes can be bred, but are less efficient.
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| References |
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Original: |
J:81238
Monani UR et al.,
"A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy."
J Cell Biol 2003 Jan 6;160(1):41-52
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All: |
5 reference(s)
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