FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd/Smn1^{tm5(Smn1/SMN2)Mrph}/J

Stock number: 014561
Product name: Burgheron
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

This virtual strain is no longer available. Search the JAX Mice database for other mouse models useful for studying Spinal Muscular Atrophy.

Detailed description

Stock No. 014561 breeding pairs allow a researcher to generate FVB.SMN2;Smn1^-/C mice; the FVB/NJ-congenic Burgheron SMA model strain with one copy of the Tg(SMN2)89 transgene and are compound heterozygous at the Smn1 locus for the Smn1 null allele and Smn1 allele C (Smn1^-/C).

Compound heterozygous (Smn1^-/C) animals harbor the Smn1 null targeted mutation (Smn1^tm1Msd; also called Smn1^-) on one homologous chromosome, and the Smn1 allele C (Smn1^{tm5(Smn1/SMN2)Mrph}; also called Smn1^C) on the other homologous chromosome. Smn1^-/C mice have an intermediate level of SMN expression that falls between that of Smn1^-/- and Smn1^C/C.

The phenotype of FVB.SMN2;Smn1^-/C mice is the intermediate type II/III Spinal Muscular Atrophy. Mean survival is ~98.5 days for females and ~102 days for males. Tail necrosis leads to tail loss by ~45 days of age. Other characteristic SMA phenotypes in the Burgheron model include cardiomyopathy, reduced numbers of functional motor units, and delayed neuromuscular junction maturation.

The phenotype of the parental mouse lines used to generate FVB.SMN2;Smn1^-/C mice (Stock No. 014561) are each briefly described below.

FVB/N-congenic mice homozygous for the Tg(SMN2)89 transgene (SMN2+/+), and homozygous for the Smn1^tm1Msd mutation (Smn-/-) are a severe Type I SMA mouse model (Stock Nos. 005024 and 007949). FVB.SMN2+/+;Smn-/- mice exhibit perinatal and complete embryonic lethality that worsens with increased backcross generations onto FVB/NJ. Also note, Stock No. 005024 does not survive as hemizygous for the Tg(SMN2)89 transgene and homozygous for the Smn1 null allele.

The Smn1^C hybrid allele contains two tandem Smn1/SMN2 genes. Homozygous FVB/N-congenic Smn1^C/C mice (Stock No. 008604) exhibit a mild SMA phenotype due to the preferential splicing of the Δ7-SMN gene product over the full-length SMN product.

Development

FVB.SMN2;Smn1^-/C mice harbor the Tg(SMN2)89 transgene and are compound heterozygous for the the Smn1 null allele and Smn allele C. The Jackson Laboratory will not distribute animals with this genotype. Instead, we will distribute as the following breeding pair: females homozygous for the Tg(SMN2)89 transgene (SMN2+/+) and heterozygous for the Smn1^tm1Msd null allele (Smn+/-) and males heterozygous for the Smn1^{tm5(Smn1/SMN2)Mrph} allele (Smn1^C/+). Each component is described below.

The creation of the Tg(SMN2)89 transgene (SMN2) and Smn1 null targeted mutation (Smn1^tm1Msd; also called Smn1^-) are described for the severe type I SMA mouse model on an FVB/NJ fully congenic background; Stock No. 007949. Note the Tg(SMN2)89 transgene insertion site in on chromosome 6. Stock No. 007949 is bred to and maintained upon an FVB/NJ-congenic background.

The creation of the Smn1 allele C (Smn1^{tm5(Smn1/SMN2)Mrph}; also called Smn1^C) is described as Stock No. 008604. Briefly, the Smn1^C contains two tandem Smn1/SMN2 genes. Stock No. 008064 is maintained upon an FVB/NJ-congenic background.

Allele

Symbol: Smn1^tm1Msd
Name: targeted mutation 1, Michael Sendtner
MGI accession ID: MGI:2183946
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Smn1
Marker name: survival motor neuron 1
Chromosome: 13
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: The expression of the lacZ gene in tissues where Smn is normally expressed was noted.
Molecular note: A lacZ-neo cassette was inserted into exon 2 by homologous recombination resulting in an in-frame fusion of lacZ to exon 2. Homozygous mutant embryos were identified up to 80 hours post coitum. The expression of the lacZ gene in tissues where Smn is normally expressed was noted.

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
Marker symbol: Smn1
Marker name: survival motor neuron 1
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.

Allele

Symbol: Grm7^{Tg(SMN2)89Ahmb}
Name: transgene insertion 89, Arthur H M Burghes
MGI accession ID: MGI:2448989
Generation method: Transgenic
Attributes: Hypomorph; Inserted expressed sequence; Humanized sequence
Marker symbol: Grm7
Marker name: glutamate receptor, metabotropic 7
Chromosome: 6
Strain of origin: FVB/N
Expressed genes: SMN2,survival of motor neuron 2, centromeric,human
Site of expression: Human SMN2 protein is expressed in the tissues examined (brain, liver, spinal cord) [Stock No. 005024].
Molecular note: A 35.5 kb genomic fragment containing the human survival motor neuron 2 (SMN2) gene and promoter was used for the transgene. The transgene is ubiquitously expressed in all tissues examined by Northern blot analysis. Line 89 carries 1 copy of the transgene integrated into intron 4 of the gene. RT-PCR confirmed reduced expression of the gene the transgene is integrated into.