Harald Jockusch

Bielefeld University · Research Field of Molecular and Cell Biology

In human globozoospermia, round-headed spermatozoa lack an acrosome and can therefore not properly interact with oocytes. In the wobbler (WR) mouse, an L967Q missense mutation in the vesicular protein-sorting factor VPS54 causes motor neuron degeneration and globozoospermia. Although electron microscopy of WR testis shows all major components of sp...

Myotonia is a symptom of various genetic and acquired skeletal muscular disorders and is characterized by hyperexcitability of the sarcolemma. Here, we have performed a comparative proteomic study of the genetic mouse models ADR, MTO and MTO*5J of human congenital myotonia in order to determine myotonia-specific changes in the global protein comple...

The clonal structure of the pancreas was analysed in neonatal and adult mouse chimeras in which one partner displayed cell patches expressing green fluorescent protein (eGFP). Coherent growth during pancreatic histogenesis was suggested by the presence of large eGFP-labelled acinar clusters rather than a scattered distribution of individual labelle...

Tumor necrosis factor alpha (TNF-alpha) is a potent cytokine in neurodegenerative disorders, but its precise role in particular brain disorders is ambiguous. In motor neuron (MN) disease of the mouse, exemplified by the model wobbler (WR), TNF-alpha causes upregulation of the metalloprotease-disintegrin ADAM8 (A8) in affected brain regions, spinal...

Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel e...

The authors describe their lives as a scientist couple, extending over more than 40 years. They worked in related, but not identical fields of molecular cell biology and biomedicine, in many different places, and raised two sons. Although this life demanded frequent compromises, they consider this as a gain rather than a loss and conclude that they...

Erbfaktoren und EiweißmoleküleKristalle des Lebens: Ordnung im UrschleimStrukturen bauen sich selbst: Ordnung und StabilitätDer Beitrag einzelner Aminosäurereste zur Proteinfunktion und ProteinstabilitätMuskel: Überkristall und molekulare MaschineIonenschleusen: Schalter in der ZellmembranDie Körpergestalt: Ordnung durch Genschalter und Zell-Zell-S...

Tissue engineering of skeletal muscle from cultured cells has been attempted using a variety of synthetic and natural macromolecular scaffolds. Our study describes the application of artificial scaffolds (collagen sponges, CS) consisting of collagen-I with parallel pores (width 20-50 microm) using the permanent myogenic cell line C(2)C(12). CS were...

Green fluorescent protein (GFP) and its variants, small, highly soluble proteins, are routinely used as reporters for patterns of gene expression and the origin of cells in transplantation experiments. When not linked as fusion proteins to other polypeptides, they distribute rapidly in the cytoplasm of a given cell, thus allowing real-time observat...

Duchenne muscular dystrophy is the most commonly inherited neuromuscular disorder in humans. Although the primary genetic deficiency of dystrophin in X-linked muscular dystrophy is established, it is not well-known how pathophysiological events trigger the actual fibre degeneration. We have therefore performed a DIGE analysis of normal diaphragm mu...

Vacuolar-vesicular protein sorting (Vps) factors are involved in vesicular trafficking in eukaryotic cells. We identified the missense mutation L967Q in Vps54 in the wobbler mouse, an animal model of amyotrophic lateral sclerosis, and also characterized a lethal allele, Vps54(beta-geo). Motoneuron survival and spermiogenesis are severely compromise...

A simple weakly frequency dependent model for the dynamics of a population with a finite number of types is proposed, based upon an advantage of being rare. In the infinite population limit, this model gives rise to a non-smooth dynamical system that reaches its globally stable equilibrium in finite time. This dynamical system is sufficiently simpl...

In order to study the pattern of clonal myocyte distribution during mammalian heart development, we have exploited embryo aggregation chimeras using, as cellular markers, an enhanced jellyfish green fluorescent protein (eGFP) transgene and a desmin-promoter-driven, nuclear-localized beta-galactosidase (nlacZ) knock-in. In neonatal, weanling, and ad...

From the viewpoint of mathematical topology, membrane systems in intact living cells can be described as closed and orientable surfaces, i.e., as surfaces with two sides and no boundary lines so that an ‘inside’ and an ‘outside’ can be distinguished. Usually, biomembranes represent topological spheres, often one embedded in another one. Toroidal me...

The antimyotonic activity of chiral derivatives of mexiletine and tocainide, selected as potent use-dependent blockers of skeletal muscle sodium channels, was evaluated in vivo acutely in myotonic ADR mice. The compounds had either aromatic (Me4 and Me6) or branched isopropyl groups (Me5 and To1) on the asymmetric centre, or had this latter one met...

To study the relative contributions of clonal coherence vs. myoblast intermingling to the formation of mammalian skeletal muscles, enhanced green fluorescent protein (eGFP) and nLacZ labels were used to analyze neonatal and adult mouse embryo aggregation chimeras. The eGFP marker allowed us to estimate absolute levels of the eGFP transgenic parenta...

We show here, by high resolution sodium dodecyl sulfate gel electrophoresis, that the proportions of myosin heavy chain (MyHC) isoforms of mouse muscles are specifically shifted by hereditary neuromuscular diseases. In wild-type and dystrophic MDX anterior tibial muscle (TA) about 60% of the MyHC is IIB, 30% IIX, at most 10% IIA and <2% type I (slo...

Muscular dysgenesis (mdg) in the mouse is a loss-of-function mutation of the skeletal muscle isoform of the voltage-sensor Ca2+ channel of skeletal muscle (DHP receptor alpha1 subunit, Cchl1a3, Chr1), which is essential for excitation-contraction coupling. Affected individuals (genotype mdg/mdg, phenotype MDG) are unable to breathe and die perinata...

The effect of IgG purified from the sera of healthy persons and patients with primary biliary cirrhosis (PBC) and chronic hepatitis (CH) on ADP dependent respiration (oxidative phosphorylation) in skinned muscle fibers from rat oxidative muscles (heart and M. soleus) and glycolytic skeletal muscle (M. gastrocnemius) was studied. The results show th...

products of the dystrophin gene range from the 427-kDa full-length dystrophin to the 70.8-kDa Dp71. Dp427 is expressed in skeletal muscle, where it links the actin cytoskeleton with the extracellular matrix via a complex of dystrophin-associated proteins (DAPs). Dystrophin deficiency disrupts the DAP complex and causes muscular dystrophy in humans...

Mutant tobacco mosaic virus (TMV) coat proteins (CPs) with known amino acid replacements provide well defined examples of destabilized tertiary structures. Here we show that misfolded TMV CPs, but not functional wild-type CPs, induce massive ubiquitylation in tobacco cells and that denatured, insoluble CP subunits are the main substrates of ubiquit...

We studied the migratory behaviour of adult muscle precursor cells in the mouse into and from skeletal muscle grafts using green fluorescent protein (GFP) and nuclear LacZ transgenes as complementary and double markers of the cell's origin. Owing to the small molecular mass and extreme solubility of GFP, this label provided a drastically increased...

Green fluorescent protein (GFP) and its variants, such as enhanced GFP (EGFP), have been introduced into mammalian cells by transgenes, e.g., to distinguish donor from host cells after transplantation. Free GFP is extremely soluble and leaks out from liquid-covered cryostat sections so that fixation of whole organs before sectioning has been mandat...

From the viewpoint of mathematical topology, membrane systems in intact living cells can be described as closed and orientable surfaces, i.e., as surfaces with two sides and no boundary lines so that an 'inside' and an 'outside' can be distinguished. Usually, biomembranes represent topological spheres, often one embedded in another one. Toroidal me...

ADAMs (a disintegrin and metalloprotease domains) are metalloprotease and disintegrin domain-containing transmembrane glycoproteins with proteolytic, cell adhesion, cell fusion, and cell signaling properties. ADAM8 was originally cloned from monocytic cells, and its distinct expression pattern indicates possible roles in both immunology and neuropa...

Dystrophin, the protein which is absent or non-functional in Duchenne muscular dystrophy, consists of four main domains: an N-terminal actin binding domain, a rod shaped domain of spectrin-like repeats, a cysteine-rich domain and a unique C-terminal domain. In muscle, dystrophin forms a linkage between the cytoskeletal actin and a group of membrane...

To support the positional cloning of the mouse mutation wobbler (wr) the corresponding regions on human Chr2p13-14 and mouse Chr11 were analyzed in detail and compared with respect to gene content, order, and orientation. The gene content of the investigated regions was highly conserved between the two species: 20 orthologous genes were identified...

The mouse mutant "motoneuron disease 2" (MND2, mnd2 on Chr 6) was originally characterized as a spinal muscular atrophy (SMA) because degenerating motoneurons were observed in late stages of the disease. MND2 mutants exhibit a progressive phenotype with neurological symptoms that begin at postnatal day (dP) 20 and include involuntary movements, abn...

The autosomal recessive mutation wobbler of the mouse (phenotype WR; genotype wr/wr) causes muscular atrophy due to motoneuron degeneration with 100% penetrance on the standard Mus musculus laboratorius C57BL/6J background. In inter- and backcrosses with M. m. castaneus strain CAST/EI we have observed a variability in the severity of neurological s...

Searching for the structural requirements improving the potency and the stereoselectivity of Na+ channel blockers as antimyotonic agents, new derivatives of tocainide, in which the chiral carbon atom is constrained in a rigid α-proline or pyrrolo-imidazolic cycle, were synthesized as pure enantiomers. Their ability to block Na+ currents, elicited f...

On Mar 5, 2004 this sequence version replaced gi:16518393.

The expression of a transgene NI-ROSA LacZ (LacZtg) trapped into the genes for two presumably untranslated, ubiquitously expressed RNAs, was studied in preimplantation mouse embryos with respect to penetrance (fraction of expressing embryos) and to localisation of beta-galactosidase activity. With maternal origin in NMRI mice beta-galactosidase was...

We analyzed, with respect to heat shock proteins (HSPs), systemically reacting tobacco leaves inoculated with Tobacco mosaic virus (TMV), wild-type vulgare, and temperature-sensitive coat protein (CP) mutants Ni 118 (P20L) and flavum (D19A), kept at 23 or 30 degrees C. HSP18 and HSP70 mRNAs and proteins were induced with temperature-sensitive CP mu...

The potential role of dystrophin-mediated control of systems integrating mitochondria with ATPases was assessed in muscle cells. Mitochondrial distribution and function in skinned cardiac and skeletal muscle fibers from dystrophin-deficient (MDX) and wild-type mice were compared. Laser confocal microscopy revealed disorganized mitochondrial arrays...

Myogenesis involves the determination of progenitor cells to myoblasts, their fusion to yield multinuclear myotubes, and the maturation of myotubes to muscle fibres. This development is reflected in a time pattern of gene expression, e.g. of genes coding for desmin, the myogenic factors myogenin and myoD, the acetylcholine receptor alpha-subunit an...

K(V)3.4 belongs to the shaw subfamily of shaker-type potassium channels. It conducts fast inactivating, high threshold currents in the central nervous system and in fast-twitch skeletal muscle fibers. The corresponding mouse gene, Kcnc4, consists of five exons spanning a region of 20 kb. Approximately 700 bp of regulatory sequence were delineated....

We have investigated the physiological role of desmin in skeletal muscle by measuring isometric tension generated in skinned fibres and intact skeletal muscles from desmin knock-out (DES-KO) mice. About 80% of skinned single extensor digitorum longus (EDL) fibres from adult DES-KO mice generated tensions close to that of wild-type (WT) controls. We...

ADAM proteases, defined by extracellular disintegrin and metalloprotease domains, are involved in protein processing and cell-cell interactions. Using wobbler (WR) mutant mice, we investigated the role of ADAMs in neurodegeneration and reactive glia activation in the CNS. We found that ADAM8 (CD 156), a suspected leukocyte adhesion molecule, is exp...

Reactive astrocytes occurring in response to neurodegeneration are thought to play an important role in neuronal regeneration by upregulating the expression of extracellular matrix (ECM) components as well as the ECM degrading metalloproteinases (MMPs). We examined the mRNA levels and cellular distribution of membrane type matrix metalloproteinase...

We identified a novel gene family in vertebrates which is preferentially expressed in developing and adult striated muscle. Three genes of the Popeye (POP) family were detected in human and mouse and two in chicken. Chromosomal mapping indicates that Pop1 and Pop3 genes are clustered on mouse chromosome 10, whereas Pop2 maps to mouse chromosome 16....

The YPT1/RAB1 protein, a key regulator of the intracellular vesicle transport in eukaryotes, is highly conserved in function and amino acid sequence. Here we report that the most highly conserved nucleotide sequence of the Rab1a gene of amniote vertebrates corresponds to the 3'-untranslated region (3'-UTR) of the mRNA. Sequences of 27 species rangi...

Titin, also called connectin, is a giant muscle protein that spans the distance from the sarcomeric Z-disc to the M-band. Titin is thought to direct the assembly of sarcomeres and to maintain sarcomeric integrity by interacting with numerous sarcomeric proteins and providing a mechanical linkage. Since severe defects of such an important molecule a...

For reconstruction or repair of damaged tissues, an artificially regulated switch from proliferation to differentiation would be of great advantage. To achieve conditional myogenesis, we expressed MyoD in mouse C3H 10T1/2 fibroblastic cells, using a gene regulation system based on the synthetic steroid RU 486. By stable co-transfection of a plasmid...

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by the loss of alpha-motoneurons in the spinal cord followed by atrophy of skeletal muscles. SMA-determining candidate genes, SMN1 and SMN2, have been identified on human chromosome 5q. The corresponding SMN protein is expressed ubiquitously. It is coded by seven exons a...

THE wobbler mouse (phenotype WR; genotype wr/wr) has been investigated as a model for neurodegenerative diseases like SMA and ALS. A new diagnostic marker based on a polymorphism in the closely linked chaperonine gene Cct4 enabled us to diagnose the allelic status at the wr locus within the original background strain C57BL/6. Using this marker, we...

To detect cation channels, the expression of which is dependent on the physiological state of muscle, single-channel activities of dissociated fibres of the mouse interosseus muscle were recorded using the patch-clamp technique in the cell-attached mode. Fibres were prepared from juvenile and adult wild-type (WT), from chloride channel-deficient my...

Chloride currents (I(Cl)) were investigated with the two-electrode voltage-clamp technique in enzymatically isolated fibers from interosseus muscles of wild-type (WT), denervated WT, and myotonic (ADR, ClC-1-deficient) mice. Characteristics of I(Cl) were consistent with previous observations on rat muscle fibers and cultured nonmuscle cells transfe...

To detect cation channels, the expression of which is dependent on the physiological state of muscle, single-channel activities of dissociated fibres of the mouse interosseus muscle were recorded using the patch-clamp technique in the cell-attached mode. Fibres were prepared from juvenile and adult wild-type (WT), from chloride channel-deficient my...