Non-human animals expressing humanized c1q complex
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsBrinda Prasad, Naxin Tu, Karolina Meagher, Lynn Macdonald, Andrew Murphy, Sean Stevens
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Abstract
Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.
Claims59
A genetically modified rodent comprising in its genome a nucleic acid encoding a chimeric C1q polypeptide, the nucleic acid comprising a rodent nucleic acid sequence and a human nucleic acid sequence,
- wherein the chimeric C1q polypeptide is selected from the group consisting of a chimeric C1qa polypeptide, a chimeric C1qb polypeptide, and a chimeric C1qc polypeptide, and
- wherein the chimeric C1q polypeptide comprises a globular head domain that is substantially human and an N-terminal stalk-stem region that is substantially rodent.
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A method of making a genetically modified rodent, comprising modifying a rodent genome such that the modified rodent genome comprises a nucleic acid encoding a chimeric C1q polypeptide, the nucleic acid comprising a rodent nucleic acid sequence and a human nucleic acid sequence,
- wherein the chimeric C1q polypeptide is selected from the group consisting of a chimeric C1qa polypeptide, a chimeric C1qb polypeptide, and a chimeric C1qc polypeptide, and
- wherein the chimeric C1q polypeptide comprises a globular head domain that is substantially human and an N-terminal stalk-stem region that is substantially rodent.
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An isolated nucleic acid, comprising one or more of a first, second or third nucleotide sequences, wherein:
- a. the first nucleotide sequence encodes a chimeric C1qa polypeptide,
- b. the second nucleotide sequence encodes a chimeric C1qb polypeptide, and
- c. the third nucleotide sequence encodes a chimeric C1qc polypeptide,
- wherein each of the first, second, and third nucleotide sequences comprises a rodent nucleic acid sequence and a human nucleic acid sequence, wherein the human nucleic acid sequence encodes substantially the globular head domain of a human C1qa, C1qb, and C1qc polypeptide, respectively, and the rodent nucleic acid sequence encodes substantially the N-terminal stalk-stem region of a cognate rodent C1qa, C1qb, and C1qc polypeptide, respectively.
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Dependencies are inferred from the claim text.