Homozygotes can usually be identified at 14 days of age by a tremor and smaller than normal body size. Most homozygotes die around 3 weeks of age, although some have lived longer.
The mutation tremor and reduced life span (trls) arose spontaneously at The Jackson Laboratory in the strain BKS.Cg-m +/+ Leprdb/J in 2000. Because homozygotes are not suitable breeders, this mutant subline was maintained by breeding hosts of homozygous ovarian transplant with donor sibling males. This was done for 10 generations before being maintained by ovarian transplant backcross-intercross to C57BLKS/J. In 2005 this strain reached generation F10N4 and the misty (m) and diabetic (Leprdb) mutations have not been seen since the initial generation so it is expected that they have been bred out.
|Allele Name||tremor and reduced lifespan|
|Gene Symbol and Name||Hcn2, hyperpolarization-activated, cyclic nucleotide-gated K+ 2|
|Strain of Origin||BKS.Cg-Dock7m +/+ Leprdb/J|
|Molecular Note||This spontaneous mutation has a G-to-A transition at chromosome 10 position 79,724,780 (GRCm38) that causes an arginine to glutamine substitution at residue 315 (p.R315Q).|