Similar to Stock No. 005024, mice that are homozygous for the targeted mutant Smn1 allele and carry the SMN2 transgene exhibit symptoms and neuropathology similar to patients afflicted with type I proximal spinal muscular atrophy (SMA). As an addition to Stock No. 005024, this line carries a transgene containing a Green Fluorescent Protein (GFP) under the direction of the mouse Hlxb9 promoter. Transgenic mice display distinct expression of GFP in dendrites, axons and soma of spinal motor neurons, allowing identification, isolation and purification of spinal motor neurons by FACS. GFP expression mimics endogenous HLXB9 expression pattern. Fluorescence is detected in axons, dendrites and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice. This mutant mouse strain represents a model that may be useful for purification and in vivo tracking of spinal motor neurons. Mice homozygous for the Hlxb9-GFP transgenic insert are reportedly viable, fertile, do not display any gross behavioral abnormalities, but are smaller in size than wild-type littermates. Homozygous pups born to homozygous females have a high mortality rate. In the initial characterization by the donating investigator, mice that are homozygous for the targeted mutant Smn1 allele and carry the SMN2 transgene exhibit symptoms and mice were either stillborn or survived 4-6 days. Mice that died at or shortly after birth were slightly smaller (1.33 g. vs. 1.51 g.) than normal littermates. Mice that survive for several days are indistinguishable from normal littermates in the first 48 hours, after which they exhibit decreased suckling and movement, labored breathing and tremoring limbs. Mice succumbing at this later time point are noticeably smaller than normal littermates (1.47 g vs. 4.59). A bell-shaped trunk is also noticeable in affected mice, presumably from intercostal muscle weakness, a characteristic of type I SMA. Histological analysis indicates that affected mice that survive to day 5 exhibit a loss of motor neurons from spinal cord (35%) and facial nucleus (40%). A large number of cells with pyknotic nuclei are observed in these tissues. Immunohistochemical analysis indicates low-level expression of the SMN2 protein in the tissues examined (brain, liver, spinal cord) and an absence or near absence of intranuclear aggregates of the SMN protein (gems?). Homozygous mice bearing the Smn1 targeted mutation without a copy of the SMN2 transgene display an embryonic lethal phenotype with developmental arrest occurring prior to implantation.
Also note, Stock No. 005024 does not survive as hemizygous for the Tg(SMN2)89 transgene (SMN2+/-) and homozygous for the Smn1tm1Msd mutation (Smn-/-).
Distribution of this model is supported by the Spinal Muscular Atrophy Foundation.
