Gne deletion in adult mice can cause thrombocytopenia, anemia, myopathy, bleeding, and death
Year: 2025
Type: article
Abstract: The GNE gene encodes the UDP-GlcNAc-2-epimerase/ManNAc kinase, a bifunctional enzyme required for the synthesis of sialic acid. The mouse Gne gene is essential for embryonic development, but humans with recessive partial loss of function GNE mutations can develop infantile thrombocytopenia, juvenile amyotrophic lateral sclerosis, or adult-onset myopathy (GNE myopathy). We have created inducible Gne lox/lox gene deletion mice to study how loss of Gne in adult mice relates to these disease states. Systemic Gne gene deletion in tamoxifen-treated Rosa- CreER T2 /Rosa- CreER T2 Gne lox/lox mice caused uniform fatality within 30 days of gene deletion with spontaneous bleeding, thrombocytopenia, and anemia. Skeletal myofiber-specific Gne deletion in tamoxifen-treated HSA- CreER T2/+ Gne lox/lox mice had no bleeding and no muscle pathology at 60 or 270 days post-treatment. Intramuscular injection of AAV.MCK. GFP-Cre in Gne lox/lox mice also showed little to no evidence of muscle pathology, while AAV.CMV. GFP-Cre caused extensive muscle damage, reduced muscle force, and changed expression of markers for muscle regeneration, muscle cell senescence, muscle denervation, and muscle atrophy. These data demonstrate that Gne is an essential gene in adult mice that can mimic aspects of human hematologic and muscle diseases caused by GNE mutations, but suggests induction of muscle disease requires loss of gene GNE expression in cell types beyond skeletal myofibers.
Authors: Patricia Lam, Deborah A Zygmunt, Macey Bennett, Anna Ashbrook, Jessica Hefty, Paul T Martin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Award: G748161538
OpenAlex ID: W4417509892