Neuroscience Mouse Models

 

 

Our catalog of KO mice contains numerous models displaying characteristics of neurodegenerative diseases or pain that you can appreciate, thanks to a panel of phenotyping tests mandated by the International Mouse Phenotyping Consortium (IMPC) and systematically performed on our lines.

Neurology-related tests:

Examples of phenotyped KO lines with neurological phenotypes:

Aldh2, Atn1, Bex2, Brd7, Cib2, Coq2, Cpe, Ect2, Emc10, Fgf10, Golga3, Herc3, Lsm1, Marveld2, Mier1, Nptn, Nxn, Otub1, Pcx, Pitx2, Prkaa2, Ramp1, Sarnp, Synj1…

 

KO of genes associated with neurological syndromes

Example 1:

Allele C of the human gene CLU was identified as a risk factor for late-onset Alzheimer’s disease (AD) (1,2). KO mice for Clu, a model of AD (3), show significant differences with WT in 2 behavioral/neurological tests performed under the IMPC guidelines:

a) Abnormal locomotor activation (transfer arousal assessed by CSD)

Figure 1a - KO with neurological syndromes

b) Increased aggression in females (assessed by CSD)

Figure 1b - KO with neurological syndromes

Example 2:

Mutations in the human gene DNAJC6 are associated with a form of early-onset Parkinson’s disease (PD) (4). KO mice for Mier1, transcriptional regulator and neighbor gene of Dnajc6, show significant differences with WT in 7 tests performed under the IMPC guidelines, including:

a) Exhibition of tremors (assessed CSD)

Figure 2a - KO with neurological syndromes

b) Abnormal behavior (measured on open field tests; whole arena permanence time)

Figure 2b - KO with neurological syndromes

 

KO exhibiting abnormal learning/memory/conditioning,
a phenotypic similarity to Alzheimer’s disease

About 45 mouse lines KO for genes such as Abca13, Cox5b, Dact2, Dst, Eml2, Gpc4, Igfbp7, Muc5ac, Pkia, Taf6...

Example 3:

a) Increased exploration in new environment in tubulin-binding protein Eml2-/- mice (transfer arousal assessed by CSD)

Figure 1a - KO with abnormal learning-memory conditioning

 

b) Expression data are also available for some lines, including Eml2-/+ mice, showing strong LacZ expression in the brain

Figure 1b - KO with abnormal learning-memory conditioning

KO exhibiting abnormal sensory capabilities/reflexes/nociception,
a phenotypic similarity to pain disorders

Figure - KO with abnormal sensory capabilities

 

About 176 mouse lines KO for genes such as Ajap1, Cib2, Elmod1, Fbxo2, Pdss2, Prdm14, Smurf1, Tmem68, Usp2, Whrn...

 

Example 4:

Increased thermal nociception threshold (time of first response) in cytoskeleton protein Whrn-/- mice (assessed on hot plate)

References:

  1. Lambert, J.-C. et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet. 41, 1094–1099 (2009).
  2. Harold, D. et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 41, 1088–1093 (2009).
  3. DeMattos, R. B. et al. Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. 99, 10843–10848 (2002).
  4. Edvardson, S. et al. A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLoS One 7, (2012).