Mouse Strains

B6.129X1-Snap25tm1Mcw/J Mouse Strain

By May 30, 2019 October 15th, 2019 No Comments

Overview

B6.129X1-Snap25tm1Mcw/J, also known as SNAP-25 KO, is a strain of mouse model in which the SNAP-25 gene has been rendered non-functional through genetic alteration.[1]

History

Embryonic stem cells (ESCs) were taken from mice of the strain 129X1/SvJ; of these, the ones that had been successfully modified to alter the gene for SNAP-25 were injected into blastocysts from the commonly used strain C57BL/6J, creating a line of chimeras. Finally, these chimeras were crossed and backcrossed with C57BL/6J for a total of seven generations to create the current B6.129X1-Snap25tm1Mcw/J mouse.[1]

Physical Characteristics

Homozygous SNAP-25 KO mouse embryos appear unusually small around day 18 of gestation. They do not move around of their own accord like a normal embryo, and do not respond to touch or other sensory stimuli. Their skin appears “blotchy”, as a result of vascular dilation.

Dissection reveals that the muscles in their chest are thin and not organized properly. The number of muscle fiber layers is reduced, and so is innervation of the diaphragm.

Heterozygous SNAP-25 KO mice do not show any of these physical abnormalities.[1]

Behavioral Characteristics & Handling

Deficiency of the SNAP-25 gene has been associated with attention deficit hyperactivity disorder (ADHD). While there are no studies reporting ADHD-like symptoms in this particular strain, hyperkinesis (excessive movement) has been reported in the SNAP-25 deficient coloboma mouse strain.[2] Heterozygotic B6.129X1-Snap25tm1Mcw/J mice would thus be expected to exhibit the same behavioral abnormality.

Hyperkinesis has important implications for handling, as it will make the mice harder to catch and hold than a more restful strain. Researchers requiring a strain with high docility may want to avoid these mice. No data could be found on the behavioral performance of this strain in mazes.

Health Characteristics

Homozygous mice of these strain are unable to breathe independently due to their diaphragm defects (see above), and so die shortly after birth from respiratory failure. Western and Northern blot analysis shows that neither the protein SNAP-25 nor its respective mRNA are found anywhere in the brain of these mice.[1]

SNAP-25 is involved with neurotransmission. Neurons signal to one another by releasing vesicles containing neurotransmitters, which then activate receptors on the other side of a synapse. SNAP-25 is part of the SNARE complex, and so assists in bringing vesicles to the presynaptic membrane, allowing them to fuse with this membrane and release their contents into the synaptic cleft.[3]

When SNAP-25 is knocked out completely, the resultant lack of neurotransmission prevents proper development of the nervous system during the embryonic phase of the mouse’s life cycle. This explains the physical abnormalities and sensory-motor deficits in the homozygote embryo.[4]

The health of heterozygotes appears relatively normal, although their reduced SNAP-25 production may entail some neurological abnormalities (see Behavioral Characteristics above).

Major Experimental Uses

As a consequence of their SNAP-25 non-functionality, this strain is most useful to researchers focused on neurobiological research, especially research into neural development and neuromuscular disorders. Given its rapid death after birth, the homozygote is unlikely to be of interest for most behavioral research applications.

References

  1. 004863 – B6.129X1-Snap25/J. 2019. 004863 – B6.129X1-Snap25/J. [ONLINE] Available at: https://www.jax.org/strain/004863. [Accessed 12 April 2019].
  2. Wilson, MC. Coloboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder. Neurosci Biobehav Rev. 2000 Jan;24(1):51-7.
  3. SNAP25 – Synaptosomal-associated protein 25 – Homo sapiens (Human) – SNAP25 gene & protein. 2019. SNAP25 – Synaptosomal-associated protein 25 – Homo sapiens (Human) – SNAP25 gene & protein. [ONLINE] Available at: https://www.uniprot.org/uniprot/P60880. [Accessed 12 April 2019].
  4. Washbourne P1, Thompson PM, Carta M, Costa ET, Mathews JR, Lopez-Benditó G, Molnár Z, Becher MW, Valenzuela CF, Partridge LD, Wilson MC. Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nat Neurosci. 2002 Jan;5(1):19-26.

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