B6.129-Smn1^{tm5(Smn1/SMN2)Mrph}/J

Stock number: 008714
Research areas: Neurobiology Research

Description

The knock-in allele, originally termed Smn allele C, in this strain is a hybrid allele consisting of two tandem Smn1/SMN2 genes. Homozygotes show reduced SMN, smaller body size at birth, and progressive tail necrosis. This mutant mouse strain may be useful in studies of chronic pain as well as Spinal Muscular Atrophy.

Detailed description

The hybrid allele, originally termed Smn allele C, inserted in this strain contains two tandem Smn1/SMN2 genes. Total SMN protein expression measured by western blot demonstrated a significant overall reduction of SMN in the spinal cord and the liver of homozygous mice compared with their heterozygous littermates and wild type controls. Homozygous mice are viable, but significantly smaller at birth than littermate controls. Tail swelling and shortening is seen as early as post-natal day 5 and necrosis and loss of tail by 45 days of age. Tail necrosis is characterized by disorganization of muscle fiber bundles along with apparent loss of intact vasculature in the absence of an inflammatory lesion as the animals age. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy.

Importation of this model was supported by the Spinal Muscular Atrophy Foundation.

Development

This mutant mouse carries the Smn allele C, which contains two tandem Smn1/SMN2 genes. The first is a hybrid gene in which a 2.2 kb segment of mouse genome containing exons 7 and 8 of the mouse Smn1 gene was replaced with a 1.3 kb fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 gene. The second is a full 42 kb copy of the human SMN2 gene. A selection cassette located downstream from the human SMN2 polyadenylation signal was removed by FLPe expression in ES cells leaving a FRT site at the downstream junction between human and mouse DNA. Because exon 7 is derived from human SMN2, it is skipped in approximately 90% of the processed mRNA derived from both genes. The 129S6/SvEvTac X C57BL/6Tac hybrid derived ES cell line F1H4 was used. The mice were then backcrossed to C57BL/6J using a speed congenic protocol.

Allele

Symbol: Smn1^{tm5(Smn1/SMN2)Mrph}
Name: targeted mutation 5, Andrew Murphy
MGI accession ID: MGI:3794202
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: Smn allele C
Marker symbol: Smn1
Marker name: survival motor neuron 1
Marker synonyms: BCD541; C-BCD541; GEMIN1; SMA; SMA@; SMA1; SMA2; SMA3; SMA4; Smn; SMNC; SMNT; T-BCD541; TDRD16A; TDRD16B
Chromosome: 13
Strain of origin: (129S6/SvEvTac x C57BL/6NTac)F1
Expressed genes: Smn1,survival motor neuron 1,mouse, laboratory; SMN2,survival of motor neuron 2, centromeric,human
Site of expression: Smn1 is normally expressed in motor neurons, particularly in the spinal chord.
Molecular note: The allele encodes two coding sequences: the first is a hybrid gene in which a 2.2 kb segment of mouse genome containing exons 7 and 8 of the mouse Smn1 gene was replaced with a 1.3 kb fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 gene and the second is a full 42 kb copy of the human SMN2 gene. A selection cassette located downstream from the human SMN2 polyadenylation signal was removed by FLPe expression in ES cells leaving a FRT site at the downstream junction between human and mouse DNA. Because exon 7 is derived from human SMN2, it is skipped in approximately 90% of the processed mRNA derived from both genes. 2 independent clones for this allele were generated and clone A2 was used to generated mice.