Knockout Mouse Models for Kinases

 

 

Our catalog of KO mice contains numerous models targeting kinases of all groups, including AGC, CMGC and Tyrosine kinases (TK).

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 kinases:

Bmx, Btk, Cdkl2, Cdk8, Clk1, Dyrkb1, Fgfr4, Gsk3a, Mapk1, Mapk10, Ntrk2, Pdgfrb, Prkcz, Ptk6, Stk32a, Twf1…

 

Example 1:

Mutations in the DYRK1B human gene, a cell cycle regulating kinase, have been associated with a form of metabolic syndrome (1). Heterozygous KO mice for the murine homolog Dyrk1b show significant differences with WT in 2 tests performed under the IMPC guideline:

a) Decreased large unstained cell number (assessed by hematology)

Figure 1a - Mutations in the DYRK1B human gene

b) Increased neutrophil cell number (neutrophil differential count by hematology)

Figure 1b - Mutations in the DYRK1B human gene

Example 2:

In humans, mutations in the tyrosine kinase NTRK2 (or TRKB) gene are associated with obesity (2) and mood disorder (3). Heterozygous mice for their homolog Ntrk2 show significant differences with WT in 5 tests performed under the IMPC guidelines, including:

a) Increased lean body mass in Ntrk2-/+ males (assessed by DEXA)

b) Decreased pre-pulse inhibition in Ntrk2-/+ males, as % of pre-pulse inhibition (measured by the acoustic startle and pre-pulse inhibition test)

c) Expression data are also available for some lines, including Ntrk2-/+ mice, showing LacZ expression in the testis

References:

  1. Keramati, A. R. et al. A form of the metabolic syndrome associated with mutations in DYRK1B. N. Engl. J. Med. 370, 1909–19 (2014).
  2. Yeo, G. S. H. et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci. 7, 1187–9 (2004).
  3. Deo, A. J. et al. A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction. Psychiatr. Genet. 23, 47–55 (2013).