A recent study led by Ludwig-Maximilians-University Munich revealed how mutations in the gene encoding Tectonic β-propeller repeat-containing protein 2 (TECPR2) contribute to the progression of Hereditary Sensory and Autonomic Neuropathy type 9 (HSAN9). The study, published in Cell Death & Differentiation provides new insights into the molecular mechanisms underlying this fatal neurodevelopmental…

In a collaborative effort within the international CHARLIE consortium, researchers have developed a gene therapy strategy for the rare genetic metabolic disorder Glutaric Aciduria Type I (GA1) by inhibiting the enzyme Aminoadipate-Semialdehyde Synthase (AASS), reducing the accumulation of neurotoxic metabolites. GA1 is caused by pathogenic variants in the GCDH gene, which encodes glutaryl-CoA…

In a recent study published in the European Journal of Human Genetics (2025), clinicians and scientists collaborated to understand the cause of neurodevelopmental disorders (NDDs) in five patients. They were associated with extremely rare variants in WSB2, encoding a CRL substrate receptor (SR) of E3 ubiquitin ligase which had never been before linked to a human disease. Using a global genetic…

DNA stability and structure need to be preserved during life to ensure proper cellular and organismal functions. End-of-chromosome complexes, telomeres, also use maintenance mechanisms to prevent DNA damage and shortening during progressive cell divisions. This is known to be crucial for healthy aging. Researchers from the German Mouse Clinic at Helmholtz Munich have generated a mouse model with …

The lncRNA Crossfirre was identified as an imprinted X-linked gene and is transcribed antisense to the trans-acting lncRNA Firre. The Firre locus forms an inactive-X-specific interaction with Dxz4, both loci providing the platform for the largest conserved chromatin structures. Scientists from the Institute of Pharmacology and Toxicology, Technical University Munich, Germany, in collaboration…

Four Opa1 isoforms are expressed in mice, which differ in the presence or absence of cleavage sites for Oma1 and for Yme1l. Mutations in the gene OPA1 (optic atrophy) cause autosomal dominant optic atrophy (ADOA) in humans, which is associated with the selective loss of retinal ganglion cells and blindness. Missense mutations in OPA1 lead to multisystem disorders with a wide range of clinical…

On April 29th and 30th, the second F2F CHARLIE Consortium meeting took place at Helmholtz Munich, organized by the German Mouse Clinic (GMC) as research partner, and supported by INFRAFRONTIER, the European Infrastructure for Modeling Human Diseases. CHARLIE (Changing rare disorders of lysine metabolism) is an international research consortium funded by the European Union’s Horizon 2020 research…

Congenital anomalies of the kidney and the urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years and the main cause of renal replacement therapy in children. The abnormalities are present from birth, and it is due to the abnormal development of the urinary system. In only ca 10% of the affected individuals, disease-causing variants in known disease…

Genetic malformations often occur during early pregnancy and unraveling the genetic basis for the resulting disorder is challenging. Current technologies for the analysis and characterization of embryonic malformations are extremely labor intensive and time-consuming, and it often takes several years to study a single gene. Human embryos or cell cultures cannot be studied easily and therefore…

A team of scientists at the Baylor College of Medicine, the Chinese University of Hong Kong, the German Mouse Clinic and collaborating institutions analyzed the genes of patients with undiagnosed neurodevelopmental disorders (NDDs) ranging from severe to mild and conducted family studies to detect genetic mutations related to their condition. The researchers discovered that the patients had…

Mitochondrial diseases are rare and complex genetic disorders that impair energy production, often leading to deficiencies in the oxidative chain. Respiratory chain complex III (CIII) deficiencies primarily manifest in the childhood and the affected patients develop diverse clinical symptoms. In the present study, recently published in BBA – Molecular Basis of Disease, the research team of the…

Currently more than 55 million people have dementia worldwide and every year there are nearly 10 million new cases. Dementia is currently the seventh leading cause of death and one of the major causes of disability and dependency among older people globally. Alzheimer disease is the most common form of dementia and may contribute to 60–70% of cases. In age-related neurodegenerative diseases, like…

Monogenic diseases are individually rare but collectively quite common, posing a huge burden on families and society. Monogenic cardio vascular diseases encompass a wide range of phenotypes that result in coronary artery disease, heart failure, aortic dissection and malignant ventricular arrhythmias. In this new study, scientists from the German Mouse Clinic at Helmholtz Munich and colleagues…

Three approaches with a reputation for slowing aging processes have proven largely ineffective. For their study, researchers developed a new method to measure aging, which accounts for the complexity of aging in organisms.   In a new study, researchers have taken a close look at three treatment approaches that have been widely believed to slow the aging process. However, when tested in mice,…

There are no known Mendelian diseases caused by variants in RABGAP1 yet. Clinicians and Scientists either caring for patients with rare homozygous genetic variances in the gene RABGAP1 or working on the KO mouse model teamed up to find the link from the gene function to the patient’s symptoms. The study led by the Hospital of Sick Children in Canada and supported by colleagues from University of…

Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. In this study, scientists of the Research Group Epigenetics, Metabolism and Longevity, Dummerstorf and the German Mouse Clinic, Helmholtz Zentrum München, characterized the geno- and phenotypes of the mouse line Titan and tested its suitability as an…

A heart defect is the most common congenital malformation, every 100th child is born with it. These genetic disorders include subsets of inherited arrhythmias, cardiomyopathies, vascular diseases and/or structural heart defects with heterogeneous clinical presentations, variable penetrance and expression, making identification of the disease-causing genes challenging. In a global effort,…

This translational study recently published in EMBO Molecular Medicine sheds light on the UQCRH gene and mitochondrial complex III diseases. An international team led by researchers and clinicians from Helmholtz Zentrum München, Germany, Manchester Centre for Genomic Medicine, UK, Newcastle University, UK and University Hospital Salzburg, Austria, identified two cousins with a deletion in the…

In this current study scientists teamed up to unraveled the mechanistic cascade underlying cortical spreading depression (CSD) and migraine susceptibility exemplified in a mouse model of  familial hemiplegic migraine type 3 (FHM3). The results were recently published in the Journal of Clinical Investigation. With a prevalence of 10-15 % in the general population migraine is one of the most common…

In the recent study scientists of the Heinrich-Pette-Institute, Hamburg, and the University of Veterinary Medicine Hannover together with colleagues from the Imperial College London, the Helmholtz Zentrum München and the Research Center Borstel have employed a new animal model to investigate whether offspring of influenza A virus-infected mothers are more susceptible to other infections later in…

The German Mouse Clinic (GMC) has implemented the EQIPD (Enhancing Quality In Preclinical Data) Quality System in addition to a well-established ISO 9001 Quality Management System (QMS) (certified since 2014). Assessment by members of an EQIPD working group revealed compliance of the QMS at the GMC with the EQIPD standards and requirements leading to the certification in June 2021.   Poor-quality…

In this recent study, scientists from the Helmholtz Center Munich generated and extensively characterized a new mouse model for the rare neurological disorder Beta-Propeller Protein Associated Neurodegeneration (BPAN). The WDR45 (WD Repeat Domain 45) gene encodes a beta-propeller scaffold protein with a putative role in autophagy, and several pathogenic variants are the genetic cause of this…

Scientists from the University of Bonn in collaboration with colleagues from Radboud University, Nijmegen and the German Mouse Clinic showed, that Creld1, the first single gene linked to atrioventricular septal defects (AVSD) of newborn, regulates myocardial development and function in mice. Missense mutations of CRELD1 (Cysteine-Rich with EGF-Like Domains 1) were found in non-syndromic and in…

Researchers from Helmholtz Zentrum München, together with the International Mouse Phenotyping Consortium (IMPC), have uncovered a large number of novel genes controlling the mineral density of bone. Because bone mineral density (BMD) is low in patients with osteoporosis, these findings help to better understand the underlying molecular mechanisms of the disease. The new insight is important to…

In a common effort, scientists of the German Mouse Clinic and Turku University examined the immune system of genetically modified mice that develop high estrogen levels in males. Applying in vivo and molecular phenotyping approaches, the researchers showed that an imbalanced circulating estrogen to androgen ratio in male mice feminized their immune response. Furthermore, their B cell function was…

Methylations are among the most prevalent RNA modifications and multiple METTL proteins have been implicated in different types of cancers. In a recent publication in Science Advances, a team of researchers from the Helmholtz-Zentrum München and colleagues discovered the impact of the RNA-modifying enzyme METTL6 as a potential new oncogene. DNA and histone modifications control gene expression -…

Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is the neuronal isoform of ITPKs and exhibits both actin bundling and InsP3kinase activity. In addition to neurons, ITPKA is ectopically expressed in tumor cells, where its oncogenic activity increases tumor cell malignancy. This raise the question, if inhibition of ITPKA could reduce oncogenic activity. However, prior to developing ITPKA specific…

An international team of researchers lead by Helmholtz Zentrum München uncovered the molecular mechanisms that link rRNA methylation to development and disease. The study was published “Genes & Development”. Almost all cellular RNAs are covalently modified and these modifications have emerged as a crucial layer in the regulation of RNA biogenesis and functions. The mechanistic understanding how…

The role for iron in the pathogenesis of diabetes is on debate. While the consequences of excess iron in β-cell function and survival are established, the effects of iron deficiency on β-cell function and diabetes risk in humans are not yet fully understood.   In a collaborative effort scientists of the University of Utah and the German Mouse Clinic unraveled a critical role for iron-regulatory…

In a collaborative effort, scientists from the University of Zurich and the German Mouse Clinic investigated the potential of a new mouse model for the autosomal recessive rare disease methylmalonic aciduria (MMAuria). The results were recently published in BBA – Molecular Basis of Disease.   MMAuria is a rare autosomal recessive inborn error of metabolism caused by deficiency of the…

In a collaborative study, scientists from the University of Bern and the German Mouse Clinic investigated the impact of the claudin family member 12 on the blood-brain barrier function and found out, that it has different roles than forming tight junctions in the cells. The results were recently published in “Fluids and Barriers in the CNS”. The blood–brain barrier (BBB) ensures central nervous…

Ischemic stroke is a predominant cause of disability worldwide. The thrombolytic or mechanical occlusion has to be removed immediately to supply the brain with blood again. However, the reperfusion bears the risk of an acute deleterious calcium-dependent breakdown of the blood-brain barrier (BBB). The reason for the increase of calcium in the blood was unknown so far. In a collaborative effort,…

Intellectual disability (ID) is a major developmental disorder and currently it was estimated to affect around 1% of the population at average. The disease is defined by significant limitations in intellectual performance and a reduction of conceptual, social and practical skills with an onset before the age of 18. Mutations in the mammalian X chromosomal tRNA 2’-O-methyltransferase FTSJ1 cause ID…

Scientists from the Folkhälsan Research Center in Helsinki, Finland, the German Mouse Clinic and colleagues from Sweden investigated, whether the activity of the alternative oxidase of Ciona intestinalis (AOX) can bypass the OXPHOS defect and ameliorates the disease manifestations in a genetic mouse model of CIII deficiency. The results of the extensive study was published recently in EMBO…

The beta crystallin gene (CRYBB2) is an ocular structural gene and mutation in this gene can cause cataract. Interestingly, beyond its role in the eye lens it is also associated with neuropsychiatric disorders, but how this gene may contribute to the symptoms of these disorders was unknown. Scientists of the German Mouse Clinic and colleagues performed a comprehensive analysis of the behavioral…

Scientists from the Heinrich-Pette-Institute Hamburg and the University of Veterinary Medicine Hannover in collaboration with the German Mouse Clinic and several other institutes showed in this study that maternal Zika virus (ZIKV) infection during early development also affects the supposedly healthy offspring at later age. The findings were recently published in ´Nature Microbiology´. In 2015,…

To unravel whether environmental enrichment leads to a higher variation of results, scientists of the Helmholtz Zentrum München investigated the influence of enrichment on the experimental outcome of a multitude of phenotypic tests in mice. The study was recently published in `PLoS Biology `.   Adequate housing of animals is legally requested within the European Union and is required, as this…

Advanced age is a risk factor for many age related disorders, and it may enhance susceptibility for disease in the next generation. The recent joint publication of the DZNE Bonn and the German Mouse Clinic reports a reduced life span and an exacerbated development of aging traits in old father offspring compared to young father offspring. The scientists assessed two groups of mice that included…

Scientists have identified a network of genes that could play an important role in the development of metabolic diseases such as diabetes. The German Mouse Clinic, collaboration partners within the Helmholtz Center Munich and the International Mouse Phenotyping Consortium (IMPC) led the work that is published in 'Nature Communications'. The development of metabolic diseases like diabetes is a…

Paladin or Pald1 is a phosphatase-domain containing protein and was identified in two independent screens for novel regulators of angiogenesis and vascular function. In a collaboration with colleagues in Sweden, the German Mouse Clinic characterized the new Pald1−/− mouse model performing behavioral, physiological and biochemical tests. Most of the phenotypes were not altered for Pald1−/− mice,…