The parent C3H strain was developed in 1920 by Strong who crossed DBA with Bagg Albino, and then selectively bred the offspring for increased incidence of mammary tumors.
The C3H/He substrain was obtained by Heston in 1941, passed to Dickie in 1947 and then finally to Snell in 1964. Snell developed the final C3H/HeSnJ form of the lineage which then passed to the Jackson Laboratory.
Behavioral Characteristics & Handling
According to the Jackson Laboratory Handbook, mice of the C3Sn strain are “jumpy”, “curious” and are easily scared if kept in a noisy environment. It thus appears that C3Sn is more anxious than normal, and so researchers requiring a calmer mouse may want to choose a different strain. Those using C3Sn should take care not to excessively stress their mice.
They breed well and are described as good parents. Otherwise, there is little information on the behavioral characteristics of these mice. The Jackson Laboratory claims they are useful for research into ataxia, suggesting they would display movement deficits on tests such as the rotarod, but no papers could be found providing evidence of such deficits.
The main health difference between C3Sn and the other members of the C3H strain family arises from it possessing one copy of the allele Clcc1m1J for the gene chloride channel-CLIC like 1. A retrotransposon insertion into the gene disrupts mRNA splicing and leads to much lower than normal levels of the corresponding protein.
Chloride channel CLIC like 1 is a channel found in the membranes of the endoplasmic reticulum and the Golgi apparatus. Loss of this protein is associated with autosomal recessive retinitis pigmentosa, a neurodegenerative disorder in which light-sensitive cells in the eye are gradually lost. Disease severity is not as great on the C3H background as it is on the C57BL/6J background.
C3Sn also shows a reduced production of CD8 T killer cells, giving it diminished immune function and in particular a reduced ability to resist viral infection.
Major Experimental Uses
As a consequence of their Clcc1 mutation, mice of the C3Sn strain are most frequently used in research on neurological disorders, especially retinal degeneration, hearing disorders, cerebellar disorders and ataxia.
- 000661 – C3H/HeSnJ. 2019. 000661 – C3H/HeSnJ. [ONLINE] Available at: https://www.jax.org/strain/000661. [Accessed 13 September 2019].
- The Jackson Laboratory Handbook on Genetically Standardized Mice. 6th ed. 2009. [ONLINE]. Available at: http://jackson.jax.org/rs/444-BUH-304/images/JAX%20Handbook%20Genetically%20Standardized%20Mice.pdf.
- Li L, Jiao X, D’Atri I, Ono F, Nelson R, Chan C-C, et al. 2018. Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. PLoS Genet. 14(8): e1007504.