These mice possess a M743T mutation (initially designated as M712T) in exon 12 of the glucosamine (Gne) gene. Exon 12 of the Gne gene is flanked by loxP sites allowing for Cre recombinase inducible tissue-specific deletion. Glucosamine catalyzes the first 2 committed, rate-limiting steps in the biosynthesis of sialic acid and can be inactivated via feedback inhibition caused by cytosolic CMP-sialic acid levels. Mutations in this gene have been associated with the development of hereditary inclusion body myopathy (HIBM) which is an adult onset, neuromuscular disorder characterized by slow progressive muscle weakness and atrophy. The M743T mutation is commonly found in people with HIBM in Iranian-Jewish families. In these HIBM cases, the muscle fibers degenerate and develop filamentous nuclear inclusions and cytoplasmic rimmed vacuoles. HIBM is also known as GNE Myopathy (GNEM), Nonaka Myopathy, Distal Myopathy with Rimmed Vacuoles (DMRV), Inclusion Body Myopathy type 2 (IBM2), or Quadriceps Sparing Vacuolar Myopathy. Homozygous mice with this mutation do not live past P3 and have no visible milk spot. They are smaller than littermates, weighing as little as 70% the weight of controls. They exhibit subcutaneous hemorrhaging and cystic tubular dilation in the kidneys. They also have excess red blood cells in the glomeruli, Bowman space, collecting ducts, renal tubules, and urinary space. They exhibit glomerular proteinuria and defects in podocyte morphology. The postnatal lethality phenotype can be rescued by prenatal administration of sialic acid N-Acetylneuraminate (Neu5Ac) or its precursor N-Acetylmannosamine (ManNAc). Heterozygous mice display a more moderate phenotype, with less red blood cell infiltration in the kidney. These mice do not exhibit a skeletal muscle phenotype which may be due to mice and humans utilizing different forms of sialic acid. In mixed inbred strains (FVB/B6) the mice may exhibit subtle muscle phenotype such as altered glycosylation of muscle tissue (detectable by Lectin histochemistry) and increased blood creatine kinase (CK) levels in response to strenuous exercise compared to control littermates. Crossing with cre deleter mice should result in nonfunctional or near nonfunctional GNE enzyme, although this has not been tested by the donating laboratory.

These mice possess a M743T mutation (initially designated as M712T) in the Gne gene. Additionally, the exon harboring the mutation (exon 12) is floxed. These mice may have applications in studies related to neuromuscular disorder hereditary inclusion body myopathy (HIBM).

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