Hello! I'd like to investigate the vestibular impact on neurogenesis. Accordingly, I'd be interested in vestibular knocked-out mice. Does anyone know and has some experienced advantages and issues to share with me! Some interesting papers?
Hi Danica,
PMCA2 knock-out mice have a profound balance defect, but are also deaf due to loss of PMCA2 in all hair cells of the inner ear.
Mutants of Otopetrin 1 gene might be a good candidate for an isolated defect of the vestibular system: there are at least two mutant mice: "tilted" - a spontaneous mutation, and "mergulhador" - by ENU mutagenesis. Both have a defect in sense of gravity and linear motion, but I am not sure on the hearing ability....
Best, A.
Neurogenesis during development? There are many mutant strains of mice that have impaired or absent vestibular function. Some of them have mutations that cause complete loss of vestibular function by hair cell damage. An example is the shaker1 mouse, a mutation in the myo7a gene. This and other Usher1 genes cause also hearing loss and retinal damage.
Vestibular dysfunction with intact hearing is less common. The tilted and head-tilt strains bear mutations that cause otoconial defects, thus impairing macular but not crista functions. In contrast, the Jackson waltzer has abnormal semicircular canals but normal maculas.
If you want to study the effect of adult vestibular loss on adult neurogenesis, you can use other models. You can eliminate vestibular hair cells using diphteria toxin in a transgenic mouse expressing the diphteria receptor driven by the myo7a promoter (Golub et al. J Neuroscience, 32: 15093–15105, 2012). Or more easily, use vestibular toxicity to cause the vestibular loss (Saldana-Ruiz et al, JARO 14: 661–671, 2013)
Several strains have complete bilateral damage. They are characterized by a deep "waltzing" syndrome. The vestibular characterization of these strains is incomplete and I don't know which ones have been well characterized in terms of development. That is, whether vestibular function in not present at birth or is lost after normal development. The latter is true in some cases, if I recall well, but I'm unsure whether strains showing a vestibular deficient phenotype from birth have been characterized. One key question may be a difficulty in survival of vestibular deficient mice during the lactation period. You can look for strains in Jackson's database, as well as in some websites devoted to hearing genetics.
I believe that congenital absence of vestibular function is more often not diagnosed than lethal during gestation.
"With respect to humans, I think that complete absence of intrauterine vestibular reflexes is lethal,"
Why do you think they are lethal? Is there any data supporting this belief?
However, you are raising a good point: a systematic search on the information available on animals and humans with early loss or lack of development of vestibular function is needed.
Based on what I know about the vestibular system, I would assume that the outcome should be similar in humans and rodents. So I would first search for mice showing absence of development of vestibular function. I believe they exist, but I'm not completely sure. I also remember a poster on vestibular deficient children presented at the FENS Forum (Barcelona, 2012), and I think some cases were deeply deficient at birth, but unsure again.
The mouse literature contains examples of developmental absence of vestibular function. In Brn-3c-null mice, hair cells are generated but fail to grow stereocilia and degenerate. Lack of stereociliary development means that they are never able to perform mecahnorecptor transduction and send vestibular information to the brain. These animals survive and grow with complete absence of vestibular function. Ref: Xiang et al., PNAS 94: 9445-9450, 1997.
For the neurogenesis study, these animals are also deaf and have retinal problems.