Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – The nonhuman animal is a model for human disease
Reexamination Certificate
2002-05-31
2008-10-21
Weber, Jon P (Department: 1657)
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
The nonhuman animal is a model for human disease
C424S009200
Reexamination Certificate
active
07439415
ABSTRACT:
This invention provides in vivo and in vitro methods of screening for an agent or a combination of agents that reduces one or more repetitive behaviors, comprising contacting neuronal cells of an animal with a HOXB8 gene mutation with the agent combination of agents to be screened, and determining whether one or more repetitive behaviors of the animal is reduced or whether one or more biochemical correlates of repetitive behaviors is reduced, the reduction in one or more repetitive behaviors or biochemical correlates indicating an agent or combination of agents that reduces repetitive behaviors. The invention also provides method of treating a subject with repetitive behaviors, comprising administering a therapeutically effective dose of the agent or combination of agents identified by the screening method. Further provided is a population of animals with a HOXB8 gene mutation, wherein more than 30% of the animals have excessive grooming behaviors and wherein less than 10% of the animals show skeletal defects.
REFERENCES:
Pato et al. The Genetics of Obsessive-Compulsive Disorder; Current Psychiatry Reports, vol. 3, No. 2 (2001) pp. 163-168.
Stein et al. Neurobiology of the Obsessive-Compulsive Spectrum Disorders; Biol. Psychiatry, vol. 47 (2000) pp. 296-304.
Araki et al., “Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase.”Proc Natl Acad Sci USA92:160-164 (Jan. 1995).
Berridge and Fentress, “Disruption of natural grooming chains after striatopallidal lesions.”Psychobiology15(4):336-342 (1987).
Charité et al., “Ectopic Expression ofHoxb-8Causes Duplication of the ZPA in the Forelimb and Homeotic Transformation of Axial Structures.”Cell78:589-601 (Aug. 26, 1994).
Charité et al., “Regulation of theHoxb-8Gene: Synergism between Multimerizedcis- Acting Elements Increases Responsiveness to Positional Information.”Dev Biol171:294-305 (1995).
Chen, “Studies on the morphogenesis of the mouse stermun. III. Experiments on the closure and segmentation of the sternal bands.”J Anatomy87:130-149 (1953).
Chen, “Studies on the morphogenesis of the mouse sternum. I. Normal Embryonic Development.”J Anatomy86:373-401 (1952).
Chen and Capecchi, “Targeted Mutations inHoxa-9andHoxb-9Reveal Synergistic Interactions.”Dev Biol181(2):186-196 (1997).
Chisaka and Capecchi, “Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox genehox-1.5.” Nature350:473-479 (Apr. 11, 1991).
Condie and Capecchi, “Mice homozygous for a targeted disruption ofHoxd-3(Hox-4.1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis.”Development119:579-595 (1993).
Condie and Capecchi, “Mice with targeted disruptions in the paralogous geneshoxa-3andhoxd-3reveal synergistic interactions.”Nature370:304-307(Jul. 28, 1994).
Davis et al., “Absence of radius and ulna in mice lackinghoax-11andhoxd-11.” Nature375:791-795 (Jun. 29, 1995).
Deschamps and Wijgerde, “Two Phases in the Establishment of HOX Expression Domains.”Dev Biol156:473-480 (1993).
Dollé et al., “Coordinate expression of the murineHox-5complex homoeobox-containing genes during limb pattern formation.”Nature342:767-772 (Dec. 14, 1989).
Fentress, “Expressive Contexts, Fine Structure, and Central Mediation of Rodent Grooming.”Ann NY Acad Sci525:18-26 (1988).
Fromental-Ramain et al., “Hoxa-13andHoxd-13play a crucial role in the patterning of the limb autopod.”Development122:2997-3011 (1996).
Gavalas et al., “Hoxa1andHoxb1synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch.”Development125:1123-1136 (1998).
Goddard et al., “Mice with targeted disruption ofHoxb-1fail to form the motor nucleus of the VIIth nerve.”Development122:3217-28 (1996).
González-Reyes and Morata, “The Developmental Effect of Overexpressing aUbxProduct in Drosophila Embryos Is Dependent on Its Interactions with Other Homeotic Products.”Cell61:515-522 (May 4, 1990).
Graham et al., “The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development.”Development112:255-264 (1991).
Greer and Capecchi, “Hoxb8is Required for Normal Grooming Behavior in Mice.” Neuron 33:23-34 (Jan. 3, 2002).
Horan et al., “Compound mutants for the paralogoushoxa-4, hoxb-4, andhoxd-4genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed.”Genes Dev9:1667-1677 (1995).
Ichimaru et al., “5-HT1A-Receptor Subtype Mediates the Effect of Fluvoxamine, a Selective Serotonin Reuptake Inhibitor, on Marble-Burying Behavior in Mice.”Jpn J Pharmacol68(1):65-70 (May 1995).
Izpisua-Belmonte et al., “Expression of the homeoboxHox-4genes and the specification of position in chick wing development.”Nature350:585-589 (Apr. 18, 1991).
Le Mouellic et al., “Homeosis in the Mouse Induced by a Null Mutation in theHox-3.1Gene.”Cell69:251-264 (Apr. 17, 1992).
Londei et al., “Investigative burying by laboratory mice may involve non-functional, compulsive, behaviour.”Behav Brain Res94:249-254 (Aug. 1998).
Maconochie et al., “Cross-regulation in the mouseHoxBcomplex: the expression ofHoxb2in rhombomere 4 is regulated byHoxb1.”Genes Dev11: 1885-1895 (1997).
Mansour et al., “Disruption of the proto-oncogeneint-2in mouse embryo-derived stem cells: a general strategy for targeting mutations to noon-selectable genes.”Nature336:348-352 (Nov. 24, 1988).
Morata, “Homeotic genes ofDrosophila.” Curr Opin Genet Dev3:606-614 (1993).
Nelson et al., “Analysis ofHoxgene expression in the chick limb bud.”Development122:1449-1466 (1996).
Neuteboom et al., “The hexapeptide LFPWMR in Hoxb-8 is required for cooperative DNA binding with Pbx1 and Pbx2 proteins.”Proc Natl Acad Sci USA92:9166-9170 (Sep. 1995).
Njung'e and Handley, “Evaluation of Marble-Burying Behavior as a Model of Anxiety.”Pharmacol Biochem Behav38(1):63-67(Jan. 1991).
Nohno et al., “Involvement of theChox-4Chicken Homeobox Genes in Determination of Anteroposterior Axial Polarity during Limb Development.”Cell64:1197-1205 (Mar. 22, 1991).
Odenwald et al., “Expression of a homeo domain protein in noncontact-inhibited cultured cells and postmitotic neurons.”Genes Dev1:482-496 (1987).
Ogura and Evans, “Evidence for two distinct retinoic acid response pathways forHOXB1gene regulation.”Proc Natl Acad Sci USA92:392-396 (Jan. 1995).
Ogura and Evans, “A retinoic acid-triggered cascade ofHOXB1gene activation.”Proc Natl Acad Sci USA92:387-391 (Jan. 1995).
Rancourt et al., Genetic interaction betweenhoxb-5andhoxb-6is revealed by nonallelic noncomplementation. Genes Dev. 9:108-122 (1995).
Rapoport et al., “Drug Treatment of Canine Acral Lick. An Animal Model of Obsessive-Compulsive Disorder.”Arch Gen Psychiatry49(7):517-521 (Jul. 1992).
Riddle et al., “Induction of the LIM Homeobox GeneLmx1by WNT7a Establishes Dorsoventral Pattern in the Vertebrate Limb.”Cell83:631-640 (Nov. 17, 1995).
Sachs, “The Development of Grooming and Its Expression in Adult Animals.”Ann NY Acad Sci525:1-17 (1988).
Studer et al., “Genetic interactions betweenHoxa1andHoxb1reveal new roles in regulation of early hindbrain patterning.”Development125:1025-1036 (1998).
Thomas and Capecchi, “Site-directed Mutagenesis by Gene Targeting in Mouse Embryo-Derived Stem.”Cell51(3):503-512 (1987).
Valarche et al., “A 3′ remote control region is a candidate to modulateHoxb-8expression boundaries.”Int J Dev Biol41:705-714 (1997).
van den Akker et al., “Targeted inactivation ofHoxb8affects s
Capecchi Mario R.
Greer Joy M.
Ballard Spahr Andrews & Ingersoll LLP
Martin Paul C.
Weber Jon P
LandOfFree
Population of Hoxb8 mutants and uses in identifying agents... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Population of Hoxb8 mutants and uses in identifying agents..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Population of Hoxb8 mutants and uses in identifying agents... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-4017038