C57BL/6JCya-Gtpbp2^em1flox/Cya

Gtpbp2, a member of the G protein superfamily, encodes a guanosine triphosphate (GTP)-binding protein. It is involved in ribosomal homeostasis [2]. Gtpbp2 also participates in several signaling pathways, such as BMP and Wnt signaling, which are crucial for embryonic development. In Xenopus embryos, it is required for BMP signaling and mesoderm patterning, and is a positive regulator of Wnt signaling, maintaining low levels of the Wnt negative regulator Axin [3,5].

Biallelic loss-of-function variants in Gtpbp2 are associated with a neuro-ectodermal clinical presentation. Key features include prenatal onset microcephaly, tone and movement disorders, epilepsy, dysmorphic features, retinal dysfunction, ectodermal dysplasia, and brain iron accumulation [1]. Some aspects of the clinical presentation seem age-related, like brain iron accumulation appearing after childhood [1]. In a canine model, a homozygous in-frame deletion in Gtpbp2 causes non-syndromic progressive retinal atrophy [6]. In humans, mutations in Gtpbp2 lead to rare genetic diseases such as Jaberi-Elahi syndrome, characterized by intellectual disability, motor development delay, abnormal reflexes, skeletal abnormalities, and visual impairment [4].

In conclusion, Gtpbp2 is essential for ribosomal homeostasis and plays a vital role in multiple signaling pathways during development. Its loss-of-function variants are associated with various neuro-ectodermal and neurodegenerative disorders, highlighting its significance in understanding the mechanisms of these diseases.