A recent publication from the lab of Christian Haass has shown altered splicing of mouse Trem2 that is dependent upon the presence of the R47H mutation and leads to a cryptic splice site in exon 2 and a deletion of 119 nucleotides.

The MODEL-AD project has similar data demonstrating the cryptic splice site.  We are currently using Western blots and whole-brain transcriptomic analysis to assay mutant protein levels.  For now, we argue that the conclusion that “functional data derived from Trem2*R47H knock-in mice cannot be translated to humans” put forward in this paper may be premature because full-length transcripts are generated in Trem2*R47H homozygotes, albeit at reduced levels.

In parallel, we are considering alternative strategies to create Trem2 alleles to model late-onset AD.

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Article in PubMed