Related Experiment Video
Updated: Jan 22, 2026
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
HACE1 deficiency leads to structural and functional neurodevelopmental defects.
Vanja Nagy1, Ronja Hollstein1, Tsung-Pin Pai1
1IMBA (V.N., T.-P.P., P.M., A.K., I.K., R.N., J.M.P.), Institute of Molecular Biotechnology of the Austrian Academy of Sciences, VBC-Vienna BioCenter Campus, Austria; Department of Medical Genetics (J.M.P.), Life Science Institute, University of British Columbia, Vancouver, Canada; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (V.N., E.L.), Vienna, Austria; Section for Functional Genetics at the Institute of Human Genetics (R.H., F.J.K.), University of Lübeck; German Center for Cardiovascular Research (DZHK e.V.) (F.J.K.), Partner Site Hamburg/Kiel/Lübeck, Lübeck; Institute of Cellular Neurosciences (M.K.H., C.H.), University of Bonn Medical School, Germany; Centre for Neuroendocrinology (M.K.H.), Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Department of Neurophysiology and Neuropharmacology (A.C., F.J.M.Q.), Center for Physiology and Pharmacology, Medical University of Vienna, Austria; Drug Safety and Metabolism (R.N.), IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden; Division of Genetics and the Roberts Individualized Medical Genetics Center (M.A.D., E.C.B.), Children's Hospital of Philadelphia, PA; Departments of Pediatrics (M.A.D.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Institute of Human Genetics (Y.L., G.Y., B.W.), University Medical Center Göttingen, Germany; Institute of Neurology (C.H.), University College London, UK; German Center for Neurodegenerative Diseases (DZNE) (C.H.), Bonn, Germany; Zentrum für Kinder- und Jugendmedizin (G.C.K.), Neuropädiatrie, Klinikum Oldenburg, Germany; Department of Medical Genetics (E.F.P.), Faculty of Medicine, Gazi University, Ankara, Turkey; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (P.B., J.M.), Vienna, Austria.
HACE1 deficiency causes spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) by altering RAC1 activity, leading to synaptic and behavioral deficits. This study establishes a mouse model for SPPRS, revealing key molecular mechanisms.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a rare neurodevelopmental disorder.
- The genetic and molecular basis of SPPRS remains largely uncharacterized.
Purpose of the Study:
- To investigate the causal role of HACE1 deficiency in SPPRS.
- To elucidate the molecular and functional mechanisms underlying HACE1 deficiency in a mouse model.
Main Methods:
- Exome sequencing identified novel HACE1 mutations in SPPRS patients.
- Phenotypic and molecular analyses were performed on HACE1 knock-out (KO) mice and patient-derived fibroblasts.
Main Results:
- HACE1 KO mice exhibited SPPRS-like features, including enlarged ventricles and cognitive deficits.
- HACE1 deficiency altered RAC1 GTPase activity and reduced synaptic function in the hippocampus.
- Patient fibroblasts showed similar RAC1 dysregulation, confirming HACE1's role.
Conclusions:
- This study provides the first animal model for SPPRS, demonstrating HACE1 deficiency as causative.
- HACE1 deficiency leads to reduced synapse number and neuropathological features resembling SPPRS.
- The findings highlight the critical role of HACE1 in neurodevelopment and synaptic integrity.
Related Concept Videos
01:56Structural Protein Function
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
01:56Structural Protein Function
01:58Fruit Development, Structure, and Function
01:29Structure and Function of Erythrocytes
The erythrocyte plasma membrane is associated with proteins such as spectrin, which forms a flexible cytoplasmic meshwork. This meshwork allows erythrocytes to twist, turn, become cup-shaped, and regain their biconcave shape as they pass through narrow capillaries. Additionally, erythrocytes can form...
01:18Structure and Function of Platelets
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
01:21Structure and Function of Leukocytes
White blood cells protect the body...