Rescue of an aggressive female sexual courtship in mice by CRISPR/Cas9 secondary mutation in vivo

BMC Res Notes. 2018 Mar 27;11(1):193. doi: 10.1186/s13104-018-3307-8.


Objective: We had previously reported a mouse line carrying the Atypical female courtship (HoxD Afc ) allele, where an ectopic accumulation of Hoxd10 transcripts was observed in a sparse population of cells in the adult isocortex, as a result of a partial deletion of the HoxD gene cluster. Female mice carrying this allele displayed an exacerbated paracopulatory behavior, culminating in a severe mutilation of the studs' external genitals. To unequivocally demonstrate that this intriguing phenotype was indeed caused by an illegitimate function of the HOXD10 protein, we use CRISPR/Cas9 technology to induce a microdeletion into the homeobox of the Hoxd10 gene in cis with the HoxD Afc allele.

Results: Females carrying this novel HoxDDel(1-9)d10hd allele no longer mutilate males. We conclude that a brain malfunction leading to a severe pathological behavior can be caused by the mere binding to DNA of a transcription factor expressed ectopically. We also show that in HoxD Afc mice, Hoxd10 was expressed in cells containing glutamate decarboxylase (Gad1) and Cholecystokinin (Cck) transcripts, corroborating our proposal that a small fraction of GABAergic neurons in adult hippocampus may participate to some aspects of female courtship.

Keywords: CRISPR/Cas9; Genome editing; HOXD10; Hippocampus; Social behavior.

MeSH terms

  • Animals
  • CRISPR-Cas Systems*
  • Cholecystokinin / genetics
  • Courtship*
  • Female
  • Gene Expression
  • Glutamate Decarboxylase / genetics
  • Homeodomain Proteins / genetics*
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mutation*
  • Neocortex / cytology
  • Neocortex / metabolism
  • Neocortex / physiology
  • Sequence Deletion*
  • Transcription Factors / genetics


  • Homeodomain Proteins
  • Hoxd10 protein, mouse
  • Transcription Factors
  • Cholecystokinin
  • Glutamate Decarboxylase