Murine expression of a human IgA lambda locus
First Claim
1. A transgenic mouse comprising in its genome a yeast artificial chromosome (YAC), wherein the YAC contains at least a majority of the human Ig Vλ
- genes of cluster A and all the human Ig Jλ
-Cλ
segments in germline configuration, wherein the proportion of the κ and
λ
light chains expressed by said transgenic mouse resembles that found in humans, and exhibits relative proportions of <
60% κ
light chains and >
40% λ
light chains, wherein at least one endogenous κ
light chain locus of the transgenic mouse is not disrupted.
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Abstract
In humans, approximately 60% of expressed immunoglobulin light chains are of the Kappa type and 40% of the Lambda type. In mice, there is almost no expression from the Lambda locus and over 95% of light chains are of Kappa type. The present invention discloses, among other things, transgenic mice carrying most of the human Ig Lambda light chain locus in their genome. The resulting mice express light chains with Kappa/Lambda ratio similar to the human ratio. Breeding of HuIg Lamda mice to Kappa-deficient mice also is described, as well as the generation of human monoclonal antibodies from transgenic mice with human Ig Lambda locus.
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Citations
28 Claims
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1. A transgenic mouse comprising in its genome a yeast artificial chromosome (YAC), wherein the YAC contains at least a majority of the human Ig Vλ
- genes of cluster A and all the human Ig Jλ
-Cλ
segments in germline configuration, wherein the proportion of the κ and
λ
light chains expressed by said transgenic mouse resembles that found in humans, and exhibits relative proportions of <
60% κ
light chains and >
40% λ
light chains, wherein at least one endogenous κ
light chain locus of the transgenic mouse is not disrupted. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
- genes of cluster A and all the human Ig Jλ
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14. A transgenic mouse comprising in its genome a yeast artificial chromosome (YAC), wherein the YAC contains at least a majority of the human Ig Vλ
- genes of cluster A and all the human Ig Jλ
-Cλ
segments in germline configuration, and expressing human λ
light chain locus genes and endogenous κ
light chain locus genes, wherein the expression of the human λ
locus is equal to or greater than that of the endogenous κ
light chain locus, and wherein at least one endogenous κ
light chain locus of the transgenic mouse is not disrupted. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
- genes of cluster A and all the human Ig Jλ
Specification