Merck + Co., Inc.

Other

The Wellcome Trust Limited as Trustee for the Wellcome Trust

Michael S Phillips

John W Hess

Patricia Hey

Michael L Metzker

Holly A Hammond

Charles T Caskey

David L Gerhold

Yusuke Nakagawa

Yoshihiko Kawaguchi

Roger D Cox

John A Todd

Tony R Merriman

C Thomas Caskey

Rebecca C J Twells

Qingyun Liu

Rebecca Cj Twells

A novel receptor, 'LDL-receptor-related protein-5' ('LRP-5'), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.

Method of screening for modulator of LRP5 activity

A novel receptor, &ldquo;LDL-receptor related protein-3&rdquo; (&ldquo;LRP-3&rdquo;), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.

LDL-receptor

Receptor

The rat ob receptor gene has been isolated and cloned. Two different alleles have been identified: the wild-type, and the fa-allele which differs from the wild type by only one base pair. The base pair change, however introduces an MspI restriction site into the DNA sequence, and also results in an amino acid change. Also part of the invention are the receptors, vectors containing the nucleic acid encoding the receptors, host cells transformed with this gene, and assays which use the gene or protein and identify new ligands.

Rat ob-receptors and nucleotides encoding them

The ob receptor has numerous isoforms resulting from alternative splicaing; three novel isoforms, designated c&prime;, f, and g are disclosed. The nucleic acids encoding these isoforms are taught. Also part of the invention are vectors containing the nucleic acid encoding the receptors, host cells transformed with these genes, and assays which use the genes or protein isoforms.

OB receptor isoforms and nucleic acids encoding them

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Lansdale, PA, United States of America

Michael S Phillips