Functional disruption of avian immunoglobulin genes

• US 20030182675A1
• Filed: 03/22/2002
• Published: 09/25/2003
• Est. Priority Date: 03/22/2002
• Status: Abandoned Application

• Current Assignee: Synageva BioPharma Corp (Astrazeneca PLC)
• Original Assignee: Origen Therapeutics
• Inventors: Zhu, Lei, Etches, Robert J., Kay, Robert M.
• Application Number:
  US10/104,486
• Publication Number:
  US 20030182675A1
• Time in Patent Office: Days
• US Class Current: 800/19
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/30 Bird
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 2267/0381 Animal model for diseases of the hematopoietic system
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/23 from birds
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2800/30 Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

Abstract

A transgenic chicken is disclosed having disrupted endogenous immunoglobulin production. In one embodiment, a targeting construct is stably integrated into the genome of the chicken by homologous recombination in embryonic stem cells, and injection of the engineered embryonic stem cells into recipient embryos, thereby knocking out the endogenous immunoglobulin gene locus in resulting animals. The targeted disruption of the locus in embryonic stem cells is particularly useful in combination with the insertion of genetic elements encoding exogenous immunoglobulin molecules. After these chickens are cross-bred, a line of chickens is produced that has a reduction of endogenous immunoglobulin molecule production.

Claims

1. A genetic construct for disruption of endogenous immunoglobulin production in chickens comprising:

a targeting vector having at least one region of homology to a chicken immunoglobulin gene and a selectable marker.

2. The construct of claim 1, wherein the vector has at least two regions of homology and a positive selectable marker located between the regions of homology.

3. The construct of claim 2 further comprising a negative selectable marker.

4. The construct of claim 1 further comprising a telomere.

5. The construct of claim 4, wherein the at least one region of homology is to a chicken immunoglobulin heavy chain locus.

6. The construct of claim 1, wherein the chicken immunoglobulin gene is a human light chain locus.