Editor’s Pick: The importance of thorough genetic investigation of transgenic models

Reviewing Editor Jean Christophe Poncer, Ph.D. selected this paper and explains why he considers it noteworthy.

Synaptic GTPase-activating protein 1 (SYNGAP1) haploinsufficiency is associated with intellectual disability and is known to promote glutamatergic synaptogenesis. In the present study, the authors asked whether it might also affect the function of hippocampal GABAergic interneurons.

Using conditional Syngap1 knockout in medial ganglionic eminence (MGE)-derived interneurons, they report cell-subtype-specific alterations of intrinsic and synaptic properties in Nkx2.1-expressing hippocampal interneurons and impaired synaptic inhibition in pyramidal neurons. However, they serendipitously discovered that the Syngap1flox mouse strain used in this and many other previous studies contains inverted loxP sites, leading to chromosome loss and cell death during cortical development, as well as reversible inversion of the floxed sequence.

The study therefore reveals unknown consequences of SYNGAP1 haploinsufficiency in GABAergic interneurons, but also highlights the importance of thorough genetic investigation of transgenic models. 

Read the full article:

Syngap1 disruption induced by recombination between inverted loxP sites is associated with hippocampal interneuron dysfunction
Abdessattar Khlaifia, Vidya Jadhav, Marc Danik, Théo Badra, Martin H. Berryer, Alexandre Dionne-Laporte, Bidisha Chattopadhyaya, Graziella Di Cristo, Jean-Claude Lacaille, and Jacques L. Michaud