scholarly journals A Role for Vascular Deficiency in Retinal Pathology in a Mouse Model of Ataxia-Telangiectasia

2011 ◽  
Vol 179 (3) ◽  
pp. 1533-1541 ◽  
Author(s):  
Dorit Raz-Prag ◽  
Ronit Galron ◽  
Niva Segev-Amzaleg ◽  
Arieh S. Solomon ◽  
Yosef Shiloh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ataxia Telangiectasia ◽  
Retinal Pathology

scholarly journals Atrophy, oxidative switching and ultrastructural defects in skeletal muscle of the ataxia telangiectasia mouse model

2019 ◽  
Vol 132 (5) ◽  
pp. jcs223008 ◽  
Author(s):  
Valentina Tassinari ◽  
Vincenzo De Gennaro ◽  
Gina La Sala ◽  
Daniela Marazziti ◽  
Giulia Bolasco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mouse Model ◽  
Ataxia Telangiectasia

scholarly journals A novel, ataxic mouse model of Ataxia Telangiectasia caused by a clinically relevant nonsense mutation

2020 ◽  
Author(s):  
Harvey Perez ◽  
May F. Abdallah ◽  
Jose I. Chavira ◽  
Martin T. Egeland ◽  
Karen L. Vo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ataxia Telangiectasia ◽  
Nonsense Mutation ◽  
Genome Stability ◽  
Cerebellar Atrophy ◽  
Genotoxic Stress ◽  
Purkinje Neuron ◽  
Cerebellar Dysfunction ◽  
Severe Ataxia ◽  
Human Disorder

AbstractAtaxia Telangiectasia (A-T) is caused by null mutations in the genome stability gene, ATM (A-T mutated). In mice, similar null mutations do not replicate A-T’s characteristic severe ataxia with associated cerebellar dysfunction and atrophy. By increasing genotoxic stress, through the insertion of null mutations in the Atm (nonsense) and related Aptx (knockout) genes, we have generated a novel A-T mouse that first develops mild ataxia, associated with abnormal Purkinje neuron (PN) activity and decreased size, progressing to severe ataxia correlated with further reduced PN activity as well as PN loss and overall cerebellar atrophy. These mice also exhibit high incidences of cancer and immune abnormalities that are all hallmarks of the human disorder. Enabled by the insertion of a clinically relevant nonsense mutation in Atm, we demonstrate that small molecule readthrough (SMRT) compounds can restore ATM production, indicating their potential as a future A-T therapeutic.

scholarly journals A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Paul Ibbett ◽  
Srinivas V. Goverdhan ◽  
Elena Pipi ◽  
Joe K. Chouhan ◽  
Eloise Keeling ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinal Degeneration ◽  
Geographic Atrophy ◽  
Retinal Pathology

scholarly journals Reducing Mitochondrial ROS Improves Disease-related Pathology in a Mouse Model of Ataxia-telangiectasia

2013 ◽  
Vol 21 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Anthony D D'Souza ◽  
Ian A Parish ◽  
Diane S Krause ◽  
Susan M Kaech ◽  
Gerald S Shadel
Keyword(s):  
Mouse Model ◽  
Ataxia Telangiectasia ◽  
Mitochondrial Ros

Impaired insulin secretion in a mouse model of ataxia telangiectasia

2007 ◽  
Vol 293 (1) ◽  
pp. E70-E74 ◽  
Author(s):  
Philip D. Miles ◽  
Kai Treuner ◽  
Marc Latronica ◽  
Jerrold M. Olefsky ◽  
Carrolee Barlow
Keyword(s):  
Insulin Secretion ◽  
Mouse Model ◽  
Ataxia Telangiectasia ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Oral Glucose ◽  
Pronounced Increase ◽  
Glucose Levels ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

Ataxia telangiectasia (A-T) is an autosomal recessive disease caused by mutations in the A-T mutated (ATM) gene. The gene encodes a serine/threonine kinase with important roles in the cellular response to DNA damage, including the activation of cell cycle checkpoints and induction of apoptosis. Although these functions might explain the cancer predisposition of A-T patients, the molecular mechanisms leading to glucose intolerance and diabetes mellitus (DM) are unknown. We have investigated the pathogenesis of DM in a mouse model of A-T. Here we show that young Atm-deficient mice show normal fasting glucose levels and normal insulin sensitivity. However, oral glucose tolerance testing revealed delayed insulin secretion and resulting transient hyperglycemia. Aged Atm−/− mice show a pronounced increase in blood glucose levels and a decrease in insulin and C-peptide levels. Our findings support a role for ATM in metabolic function and point toward impaired insulin secretion as the primary cause of DM in A-T.

scholarly journals Oxidative stress-driven pulmonary inflammation and fibrosis in a mouse model of human ataxia-telangiectasia

Redox Biology ◽  
2018 ◽  
Vol 14 ◽  
pp. 645-655 ◽  
Author(s):  
Ruth Duecker ◽  
Patrick Baer ◽  
Olaf Eickmeier ◽  
Maja Strecker ◽  
Jennifer Kurz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Ataxia Telangiectasia ◽  
Pulmonary Inflammation
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