Neuronal ceroid-lipofuscinoses type 2 and 3 (CLN2 and 3)

Co-Project Leader: Angela Schulz

  • Research project CLN3
  • Research project CLN3

    CLN3 (Batten disease, Juvenile Neuronal Ceroid Lipofuscinosis)

    In our research group we investigate the function(s) and the intracellular trafficking of the late endosomal/lysosomal membrane protein CLN3, which is defective in juvenile neuronal ceroid lipofuscinosis (JNCL, for review see Jalanko and Braulke, 2009 ). JNCL is an autosomal recessively inherited lysosomal storage disorder and is caused by mutations in the CLN3 gene. The disease is clinically characterized by an initial visual impairment at the age of 5 to 7 years leading to final blindness, seizures, psychomotoric deterioration and premature death.

    The precise function of the CLN3 gene product is still unknown but it has been suggested to contribute to the regulation of lysosomal pH and the transport of amino acids across lysosomal membranes. Furthermore, CLN3 appears to be important for complex processes such as apoptosis, axon pruning during development, maturation of autophagosomes, modification of fatty acids, organization of the cytoskeleton and trafficking of cargo receptors. The consequences of CLN3 deficiency on lysosomal biogenesis, lysosomal functions and the development and viability of neuronal cells are largely unknown.

    Four mouse models with targeted deletion of selected exons in the orthologous CLN3 gene were generated in different laboratories which partially resemble the phenotype observed in patients with JNCL.

  • Investigation of immunreactions in CLN2-patients under treatment with recombinant TPP1 enzyme

    This part of the website is under construction. A detailed project description is coming soon.

  • Project-relevant Publications

    Original Articles:

    • Novel morphological macular findings in juvenile CLN3 disease. Dulz S, Wagenfeld L, Nickel M, Richard G, Schwartz R, Bartsch U, Kohlschütter A, Schulz A (2015) Br J Ophthalmol bjophthalmol-2015-307320 Abstract
    • Phenotyping heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with CLN3 mutations. Bergholz R, Kohlschütter A, Schulz A, Hubert W, Rüther K (2015) Graefes Arch Clin Exp Ophthalmol 253:1245-50 Abstract
    • LYSOPLEX: an efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway. Di Fruscio G*, Schulz A*, De Cegli R, Savarese M, Mutarelli M, Parenti G, Banfi S, Braulke T, Nigro V, Ballabio A (2015) Autophagy 11:928-38 (*shared first author) Abstract
    • Quantitative T2 measurements in juvenile and late infantile neuronal ceroid lipofuscinosis. Paniagua A, Forkert ND, Schulz A, Löbel U, Fiehler J, Ding X, Sedlacik J, Goebell E (2012) Clin Neurorad DOI 10.1007/s00062-012-0189-3 Abstract
    • Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. Kousi M, Anttila V, Schulz A, Calafato S, Jakkula E, Riesch E, Myllykangas L, Kalimo H, Topcu M, Göbken S, Alehan F, Lemke JR, Alber M, Palotie A, Kopra O, Lehesjoki AE (2012) J Med Genet 49:391e399 Abstract
    • Analysis of potential biomarkers and modifier genes affecting the clinical course of CLN3 disease. Lebrun AH, Moll-Khosrawi P, Pohl S, Makrypidi G, Storch S, Kilian D, Streichert T, Otto B, Mole SE, Ullrich K, Cotman S, Kohlschütter A, Braulke T, Schulz A (2011) Mol Med 17:1253-61 Abstract
    • Retention of Lysosomal Protein CLN5 in the Endoplasmic Reticulum Causes Neuronal Ceroid Lipofuscinosis in Asian Sibship. Lebrun AH, Storch S, Rüschendorf F, Schmiedt ML, Kyttällä A, Mole SE, Kitzmüller C, Saar K,, Mewasingh LD, Boda V, Kohlschütter A, Ullrich K, Braulke T, Schulz A (2009) Hum Mutat 30:E651-61 Abstract
    • The CLN9 Protein – A Regulator of Dihydroceramide Synthase. Schulz A, Mousallem T, Venkataramani M, Persaud-Sawin DA, Zucker A, Luberto C, Bielawska A, Bielawski J, Holthuis JCM, Jazwinski SM, Boustany RM (2006) J Biol Chem 281:2784-94 Abstract
    • Impaired Cell Adhesion and Apoptosis in the Novel CLN9 Batten Disease Variant. Schulz A, Dhar S, Rylova S, Ucci A, Alroy J, Hagel C, Artacho I, Lin S, Kohlschütter A, Boustany RM (2004) Ann Neurol 56:341-50 Abstract
    • Ethical issues with artificial nutrition of children with degenerative brain diseases. Kohlschütter A, Riga C, Crespo D, Torres JM, Penchaszadeh V, Schulz A (2015) Biochim Biophys Acta 1852:1253-6 Abstract
    • NCL diseases – Clinical Perspectives. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R (2013) Biochim Biophys Acta 1832:1801-6 Abstract
    • CLN2 - Clinical, diagnosis and clinical management. Kohlschütter A, Schulz A, van Diggelen O. Chapter 4 in: The Neuronal Ceroid Lipofuscinoses (Batten Disease). SE Mole, HH Goebel, R Williams, editors. IOS Press Book 2011
    • CLN3 – Diagnosis. Kohlschütter A, Schulz A. Chapter 5 in: The Neuronal Ceroid Lipofuscinoses (Batten Disease). SE Mole, HH Goebel, R Williams, editors. IOS Press Book 2011
    • CLN6 – Clinical, diagnosis and clinical management. Schulz A, Cregeen D, Kohlschütter A. Chapter 8 in: The Neuronal Ceroid Lipofuscinoses (Batten Disease). SE Mole, HH Goebel, R Williams, editors. IOS Press Book 2011

  • 01/2016 - 12/2018
    Angela Schulz & Thomas Braulke
    EU Horizon 2020
    BATCure: European network for coordinated research on neuronal ceroid lipofuscinosis

    02/2016 - 01/2019
    Angela Schulz & Thomas Braulke
    Federal Ministry of Education and Research (BMBF)
    NCL2TREAT: A network for coordinated research and development of clinical biomarkers, diagnostics, pathomechanisms and therapeutic strategies for neuronal ceroid lipofuscinoses

    BioMarin (independent research grant)
    Angela Schulz