Murine expression of a human IgA lambda locus
First Claim
1. A transgenic mouse comprising as a translocus a YAC of about 410 Kb, wherein the YAC contains most of the human Vλ
- genes of cluster A and all the human Jλ
-Cλ
segments in germline configuration, wherein the translocus shows high expression, and is able to compete equally with the endogenous mouse κ
locus.
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Accused Products
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
9 Claims
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1. A transgenic mouse comprising as a translocus a YAC of about 410 Kb, wherein the YAC contains most of the human Vλ
- genes of cluster A and all the human Jλ
-Cλ
segments in germline configuration, wherein the translocus shows high expression, and is able to compete equally with the endogenous mouse κ
locus. - View Dependent Claims (5, 6, 7, 8, 9)
- genes of cluster A and all the human Jλ
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2. A transgenic mouse comprising as a translocus a YAC of about 410 Kb, wherein the YAC contains most of the human Vλ
- genes of cluster A and all the human Jλ
-Cλ
segments in germline configuration, wherein the mouse has one or both endogenous Igκ
alleles disrupted, and wherein the translocus shows high expression.
- genes of cluster A and all the human Jλ
-
3. A transgenic mouse carrying a 380 Kb region of the human immunoglobulin (Ig) λ
- light (L) chain locus in germline configuration, wherein the introduced translocus resides on a yeast artificial chromosome (YAC) that accommodates the most proximal V (variable gene) λ
cluster—
with 15 V λ
genes that contribute to over 60% of λ
light chains in man—
and all Jλ
-Cλ
segments with the 3′
region including the downstream enhancer.
- light (L) chain locus in germline configuration, wherein the introduced translocus resides on a yeast artificial chromosome (YAC) that accommodates the most proximal V (variable gene) λ
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4. A transgenic mouse comprising human Ig lambda genes in which the proportion of the κ
- and λ
light chains expressed by said human lambda genes resembles that found in humans, and exhibits relative proportions of ≦
60% κ
light chains and ≧
40% λ
light chains.
- and λ
Specification