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

First Author  Zakany J Year  2018
Journal  BMC Res Notes Volume  11
Issue  1 Pages  193
PubMed ID  29580290 Mgi Jnum  J:259687
Mgi Id  MGI:6149366 Doi  10.1186/s13104-018-3307-8
Citation  Zakany J, et al. (2018) Rescue of an aggressive female sexual courtship in mice by CRISPR/Cas9 secondary mutation in vivo. BMC Res Notes 11(1):193
abstractText  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 HoxD(Del(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.
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