Devanney Sean C, Gibney Joseph M, Le Prell Colleen G, Wronski Thomas J, Aguirre J I, Mcdoom Issam, Heldermon Coy D
College of Medicine, Department of Medicine, University of Florida, Box 100278, Gainesville, FL 32610, United States of America.
School of Behavioral and Brain Sciences, University of Texas at Dallas, 1966 Inwood Road, room J216, Dallas, TX 75235, United States of America.
Mol Genet Metab Rep. 2021 Feb 6;27:100727. doi: 10.1016/j.ymgmr.2021.100727. eCollection 2021 Jun.
Two unique gene mutations in the enzyme beta-glucuronidase (GUSB) that result in the lysosomal storage disease Mucopolysaccharidosis (MPS) type VII had previously been reported to have differing disease phenotype severities when compared on differing mouse strains. The MPSVII mouse has proven to be a highly efficacious model to study mucopolysaccharidoses and for evaluating potential gene or stem cell therapies for lysosomal storage diseases. We examined the single base pair deletion (MPSVII) and the intracisternal A particle element insertion (MPSVII2J) in GUSB compared with control animals by skeletal measures, electroretinography, auditory-evoked brainstem response and life span on a C57BL/6J background strain. In all measures, both mutations result in either a trend toward or significant changes from the background strain control. In all measures, there is no significant phenotypic difference between the two mutations. The 2J variant is a more easily genotyped and equally affected phenotype, which holds promise for further studies of chimerism and stem cell therapy approaches.
先前有报道称,酶β-葡萄糖醛酸酶(GUSB)中的两种独特基因突变会导致溶酶体贮积病VII型黏多糖贮积症(MPS),在不同的小鼠品系中比较时,它们具有不同的疾病表型严重程度。事实证明,MPSVII小鼠是研究黏多糖贮积症以及评估溶酶体贮积病潜在基因或干细胞疗法的高效模型。我们通过骨骼测量、视网膜电图、听觉诱发脑干反应以及在C57BL/6J背景品系上的寿命,将GUSB中的单碱基对缺失(MPSVII)和池内A颗粒元件插入(MPSVII2J)与对照动物进行了比较。在所有测量中,两种突变均导致与背景品系对照相比呈趋势性变化或显著变化。在所有测量中,两种突变之间没有显著的表型差异。2J变体更容易进行基因分型且具有同样受影响的表型,这为嵌合现象和干细胞治疗方法的进一步研究带来了希望。