B6.129-Smn1^{tm4(SMN2)Mrph}/J

Stock number: 008453
Research areas: Neurobiology Research

Description

In this hybrid allele, exon 7 of Smn1 (survival motor neuron 1) is replaced with the equivalent exon from human SMN2 (survival of motor neuron 2, centromeric), and is skipped in approximately 90% of the processed mRNA. Further characterization is currently in progress. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy.

Detailed description

In this hybrid allele, exon 7 of Smn1 (survival motor neuron 1) is replaced with the equivalent exon from human SMN2 (survival of motor neuron 2, centromeric), and is skipped in approximately 90% of the processed mRNA. Further characterization is currently in progress. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy.

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

Development

This targeted mutation, Smn allele B, is a hybrid Smn1 (survival motor neuron 1) allele in which a 2.2 kb segment of mouse genome containing exons 7 and 8 of the mouse Smn1 (survival motor neuron 1) gene was replaced with a 1.3 kb fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 (survival of motor neuron 2, centromeric) 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 the hybrid allele. The 129S6/SvEvTac X C57BL/6Tac hybrid derived F1H4 ES cell line was used. The mice were then backcrossed to C57BL/6J using a speed congenic protocol.

Allele

Symbol: Smn1^{tm4(SMN2)Mrph}
Name: targeted mutation 4, Andrew Murphy
MGI accession ID: MGI:3794200
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Smn allele B
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: SMN2,survival of motor neuron 2, centromeric,human
Molecular note: A 2.2 kb segment of mouse genome containing exons 7 and 8 of the mouse Smn1 (survival motor neuron 1) gene was replaced with a 1.3 kb fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 (survival of motor neuron 2, centromeric) 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 the hybrid allele.