Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1999-12-01
2004-08-24
Landsman, Robert (Department: 1647)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S252300, C435S320100, C435S325000, C435S471000, C435S007100, C435S007200, C530S350000, C530S402000, C536S023500
Reexamination Certificate
active
06780608
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to nucleic acids and protein of the type 3 human ryanodine receptor (hRyR3), chimeric ryanodine receptors with parts of the human receptor and processes for preparing these proteins. The invention further relates to the detection of ryanodine receptors in human tissues for diagnosing pathological conditions and methods of identifying activators or inhibitors of hRyR3.
Cytoplasmic calcium plays an important part in cell activation, the release of neurotransmitters, muscle contraction and other biological processes. It is increased by the effect of extracellular calcium resulting from voltage-activated and other ion channels and by the calcium release from intracellular supplies. At present, two intracellular calcium release channels are known, the inositol 1,4,5-triphosphate receptors (IP3R) and the ryanodine receptors (RyR). The release of calcium by IP3R starts from a ubiquitous mechanism which has been described for numerous cells. By contrast, three types of RyR-mRNA, namely RyR1, RyR2 and RyR3 are expressed tissue-specifically; RyR1 primarily in the skeletal muscle, RyR2 in the heart muscle and brain and RyR3 in the brain and smooth muscle. In the brain, the RyR3 is strongly expressed only in very limited areas such as the hippocampus, Nucleus caudatus, Corpus callosum and thalamus. The RyR3 is also expressed in non-excitable cells such as human T-lymphocytes. It has been postulated that RyR3 has a part to play in cell proliferation (Hakamata, Y. et al. FEBS Lett., 352 (1994), 206-210). For RyR1 and RyR2 it has been shown that, in the excitation contraction coupling of skeletal and heart muscle, voltage-activated calcium channels activate the RyR1 in the skeletal muscle and presumably also in neurones directly, whereas the calcium of the voltage-activated channels is a trigger for the opening of RyR2 in heart muscle (calcium-induced release of calcium). The function of RyR3 is subject to a series of speculations. Although calcium appears to be an important physiological ligand of RyR3, there are some indications that the calcium-induced release of calcium differs from that of other RyR. It is assumed that an endogenous RyR3 is responsible for the substantially lower calcium sensitivity of the remaining calcium release activity of RyR1-deficient murine muscle cells. RyR3 is demonstrably insensitive to caffeine in some cases, caffeine being the substance primarily used for RyR activation. Since RyR3 is expressed in non-excitable cells which have virtually no voltage activated calcium channels, it appears possible that RyR3 is regulated by different mechanism from the other RyR. RyR3-deficient mutant mice exhibit increased locomotor activity. The cDNA sequences of RyR1, RyR2 and for rabbit-RyR3 (rRyR3) are already known whereas the nucleic acid sequence of RyR3 in humans (hRyR3) has not yet been investigated.
In spite of a plethora of bits of information regarding RyR3, its molecular physiological properties, its significance in pathological conditions and methods of evaluating possible inhibitors and activators of its activity are substantially or even totally unknown. In addition, the transfer of the currently available information from tests with isolated RyR3 of non-human origin to humans is accompanied by considerable uncertainty.
REFERENCES:
patent: WO 91/04328 (1991-04-01), None
Nakashima Y, et al. FEBS Letters 417:157-162, 1997.*
Blumenthal, D.K., et al., “Identification of the calmodulin-binding domain of skeletal muscle myosin light chain kinase,”Proc. Natl. Acad. Sci. USA 82:3187-3191 (1985).
García, J., and Beam, K.G., “Measurement of Calcium Transients and Slow Calcium current in Myotubes,”J. Gen. Physiol. 103:107-123 (1994).
Gillard, E.F., et al., “A Substitution of Cysteine for Arginine 614 in the Ryanodine Receptor Is Potentially Causative of Human Malignant Hyperthermia,”Genomics 11:751-755 (1991).
Goeddel, D.V., et al., “The structure of eight distinct cloned human leukocyte interferon cDNAs,”Nature 290:20-26 (1981).
Hakamata, Y., et al., “Primary structure and distribution of a novel ryanodine receptor/calcium release channel from rabbit brain,”FEBS Lett. 312: 229-235 (1992).
Hakamata, Y., et al., “Involvement of the brain type of ryanodine receptor in T-cell proliferation,”FEBS Lett. 352: 206-210 (1994).
Kemp, B.E., and Pearson R.B., “Protein kinase recognition sequence motifs,”Trends Biochem. Sci. 15:342-346 (1990).
Kozack M., “Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs,”Nucl. Acids Res. 12:857-872 (1984).
MacLennan, D.H., and Phillips, M.S., “Malignant Hyperthermia,”Science 256:789-794 (1992).
Maeda, A., et al., “Generation of Cell Transfectants Expressing Cardiac Calcium Ion Channel and Calcium Indicator Protein Aequorin,”Anal. Biochem. 242: 31-39 (Nov. 1996).
McPherson, P.S., and Campbell, K.P., “Solubilization and Biochemical Characterization of the High Affininty (3H)Ryanodine Receptor from Rabbit Brain Membranes,”J. Biol. Chem. 265: 18454-18460 (1990).
Moncrief, N.D., et al., “Evolution of EF-Hand Calcium-Modulated Proteins,”J. Mol. Evol. 30:522-562 (1990).
Nakai, J., et al., “Primary structure and functional expression from cDNA of the cardiac ryanodine receptor/calcium release channel,”FEBS Lett. 271:169-177 (1990).
Nakai, J., et al., “Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor,”Nature 380:72-75 (Mar. 1996).
Niidome, T., et al., “Molecular cloning and characterization of a novel calcium channel from rabbit brain,”FEBS Lett. 308:7-13 (1992).
Penner, R., et al., “Functional expression of the calcium release channel from skeletal muscle ryanodine receptor cDNA,”FEBS Lett. 259:217-221 (1989).
Takeshima, H., et al., “Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor,”Nature 339:439-445 (1989).
Weirenga, R.K., and Hol, W.G.J., “Predicted nucleotide-binding properties of p21 protein and its cancer-associated varient,”Nature 302:842-844 (1983).
Zorzato, F., et al., “Molecular Cloning of cDNA Encoding Human and Rabbit Forms of the Ca2+Release Channel (Ryanodine Receptor) of Skeletal Muscle Sarcoplasmic Reticulum,”J. Biol. Chem. 265:2244-2256 (1990).
Barsoumian Edward Leon
Hakamata Yasuhiro
Nishimura Seiichiro
Boehringer Ingelheim International GmbH
Landsman Robert
Sterne Kessler Goldstein & Fox P.L.L.C.
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