11 beta hydroxysteroid dehydrogenase type 1
AssigneeBristol-Myers Squibb Company
InventorsDavid Gordon, Yuval Blat, Akbar Nayeem, Mark S. Kirby, Bin He
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Abstract
The invention provides gene-targeted non-human animals comprising a genetically modified 11βHSD1 gene encodes a mutant 11βHSD1 polypeptide which is modulated by human 11βHSD1 modulating compounds. The invention further provides cells expressing mutant 11βHSD1 and cells isolated from gene-targeted animals, which cells produce a mutant 11βHSD1. The invention further provides methods of identifying agents that modulate 11βHSD1 activity, and are useful to treat 11βHSD1-related metabolic disorders.
Claims11
An isolated nucleic acid molecule comprising a nucleotide sequence derived from a mouse 11βHSD1 gene, wherein said nucleotide sequence encodes a modified amino acid sequence comprising a Glutamine to Tyrosine substitution at a position equivalent to amino acid 177 of the 11βHSD1 polypeptide, and wherein said modified amino acid sequence has 11βHSD1 activity.
An isolated polypeptide comprising an amino acid sequence derived from a mouse 11βHSD1 polypeptide, wherein said amino acid sequence comprises a Glutamine to Tyrosine substitution at a position equivalent to amino acid 177 of the 11βHSD1 polypeptide wherein said modified amino acid sequence has 11βHSD1 activity.
(canceled)
An isolated, gene-targeted cell comprising a modified 11βHSD1 endogenous allele, wherein said modified 11βHSD1 endogenous allele is under transcriptional control of endogenous regulatory sequences, and wherein the modified 11βHSD1 allele encodes a modified amino acid sequence comprising a Glutamine to Tyrosine substitution at a position equivalent to amino acid 177 of the 11βHSD1 polypeptide and has 11βHSD1 activity.
11-12. (canceled)
Dependencies are inferred from the claim text.