Poster Presentation 44th Lorne Genome Conference 2023

Effects of loss of the Börjeson–Forssman–Lehmann syndrome gene Phf6 on brain development (#141)

Melody PY Leong 1 2 , Helen M McRae 1 2 , Maria I Bergamasco 1 2 , Anthony J Hannan 3 4 , Tim Thomas 1 2 , Anne K Voss 1 2
  1. The Walter and Eliza Hall Institute of Medical research, Parkville, 3052, Victoria, Australia
  2. Department of Medical Biology, University of Melbourne, Parkville, 3052, Victoria, Australia
  3. Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, 3052, Victoria, Australia
  4. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, 3052, Victoria, Australia

Plant homeodomain finger protein 6 (PHF6) is a highly conserved chromatin associated
protein that is important for neurodevelopment and hematopoiesis. Inherited or de novo
mutations in the PHF6 gene cause Börjeson–Forssman–Lehmann syndrome (BFLS), a rare Xlinked
neurodevelopmental and endocrine disorder. Patients with BFLS present with
intellectual Disability (ID) which affects cognitive and adaptive functioning. To progress our
understanding of how PHF6 gene mutations affect the nervous system in BFLS, we studied
the impact of deletion of the Phf6 gene on brain development in mice.
We report the anatomical, cellular and molecular effects of loss of PHF6 on the brain in our
mouse model of BFLS. Histological and morphological analysis of the brains revealed a
significant difference in adult Phf6 mutant mice compared to wild-type littermate controls.
Transcriptional changes caused by loss of PHF6 assessed by RNA-sequencing were also
prominent. Specific cell functions were affected by loss of PHF6.
Our data provide an insight into the anatomical, cellular and molecular effects of loss of PHF6
in the developing brain in mice.