Knockout Mouse Models for Water and Ion Channels

 

 

Our catalog of KO mice contains numerous models targeting water and ion channels, voltage, ligand-gated, and others.

All our lines are submitted to a panel of phenotyping tests mandated by the International Mouse Phenotyping Consortium (IMPC) and systematically performed to identify significant phenotypes between WT and KO.

Examples of phenotyped KO lines for ion channels:

Aqp1, Aqp3, Aqp6, Grin1, Grin2d, Kcnb1, Kcne1, P2rx6,, Kcnj11, P2rx4, P2rx7…

 

Example 1:

Mutations in the human KCNB1 gene, voltage-gated potassium channel, are associated with early infantile forms of epileptic encephalopathy (1). KO mice for its homolog Kcnb1 show significant differences with WT in 4 tests performed under the IMPC guidelines, including:

a) Hyperactivity, here increased total traveled distance (assessed by open field)

Figure 1a - Mutations in the human KCNB1

b) Abnormal gait or lack of fluidity in movement for females (Combined SHIRPA and Dysmorphology [CSD])

Figure 1b - Mutations in the human KCNB1

Example 2:

KO mice for Aqp1, a water channel involved in cerebrospinal fluid secretion (2) and pain sensation (3), show significant differences with WT in 7 tests performed under the IMPC guidelines, including:

a) Impaired glucose tolerance (assessed by intraperitoneal glucose tolerance test)

Figure 1a - KO mice for Aqp1

b) Hypoactivity characterized by lower locomotor activity (CSD)

Figure 1b - KO mice for Aqp1

References:

  1. Torkamani, A. et al. De novo KCNB1 mutations in epileptic encephalopathy. Ann. Neurol. 76, 529–540 (2014).
  2. Oshio, K. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J. (2004). doi:10.1096/fj.04-1711fje.
  3. Oshio, K., Watanabe, H., Yan, D., Verkman, A. S. & Manley, G. T. Impaired pain sensation in mice lacking Aquaporin-1 water channels. Biochem. Biophys. Res. Commun. 341, 1022–1028 (2006).