Inbred miniature swine and uses thereof

Details Inbred miniature swine and uses thereof Inbred miniature swine and uses thereof

1999-08-20

2002-10-22

Nguyen, Dave T. (Department: 1632)

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

Transgenic nonhuman animal

C800S008000, C800S021000

Reexamination Certificate

active

06469229

ABSTRACT:

BACKGROUND OF THE INVENTION
The major histocompatibility complex (MHC) is a set of linked genes which code for cell surface proteins involved in transplant rejection. The MHC contains three types of genes, class I, II and III (Klein J. et al.:
Immunology
: The Science of Self-Nonself Discrimination, pp. 687, 1984, John Wiley, Somerset, N.J.).
In humans, class I genes encode polymorphic 44,000 dalton glycoprotein chains that associate with a nonpolymorphic 12,000 dalton light chain, &bgr;2-microglobulin, and which are expressed on most cells of the body. Typical class I MHC genes are involved in regulating immune to viral infections (Zinkemagal R. M. et al. (1979)
Adv. Immunol.
27:52-72).
In humans, the class II MHC antigens are cell surface glycoproteins composed of an &agr; chain of approximately 35,000 daltons and a &bgr; chain of about 28,000 that are expressed only on subsets of immunologically active cells, such as &bgr; lymphocytes and macrophages.
Class III MHC genes code for serum proteins such as complement (C′).
The MHC loci in swine are known as the swine leukocyte antigens (SLA). In 1970, Vaiman et al., (Vaiman M. et al. (1970)
Transplantation
10: 155-161) and Viza et al. (Viza D. et al. (1970)
Nature
227:949-951) provided descriptions of the SLA complex. These groups developed panels of SLA typing reagents (Vaiman M. et al. (1979)
Immunogenetics
9:353-361) by preparing antisera of defined specificity as well as by characterizing cells of known SLA type (homozygous typing cells) for use in mixed lymphocyte complex, to chromosome 7 (Geffrotin C. et al. (1984)
Ann Genet
(Parix) 27:213-219). The class I swine MHC loci are designated SLA-A,B,C. The class II swine MHC loci are designated SLA-DR, DQ. Because there are numerous genes coded by the SLA complex and because usually they are inherited as a unit, haplotype designations have been developed. For example, the SLAa haplotype codes for SLA-A
a
B
a
C
a
DR
a
DQ
a
alleles.
Miniature swine are a good model for organ transplantation studies because of their breeding characteristics which make them one of few large animals in which genetics can be manipulated in a reasonable time, and also because of their size which permits surgical manipulations similar to those humans.
SUMMARY OF THE INVENTION
The invention provides a genetically defined, large animal, useful, e.g., as an organ, tissue, or cell, donor, which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and preferably in which a sufficient number of all other genetic loci are homozygous such that an organ, tissue, or cell, from one animal can be used to prolong acceptance in a recipient, e.g., a xenorecipient, of an organ, tissue, or cell, from a second animal from a herd of such animals, or such that prolongation of acceptance (e.g., by the induction of tolerance) in a recipient, e.g., a xenorecipient, of an organ, tissue, or cell, from one animal of the herd also provides prolongation of acceptance of an organ, tissue, or cell, from a second animal of the herd.
Accordingly, the invention features, a swine, preferably a miniature swine, which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous. In preferred embodiments, at least 65%, 70%, 75%, 80%, 85%, 90%, 95% or more, of all other genetic loci in the swine are homozygous.
In preferred embodiments, the swine leukocyte antigens (SLA) A, B, C, DR, and DQ can be of haplotype a (A
a
, B
a
, C
a
, DR
a
, DQ
a
), haplotype c (A
c
, B
c
, C
c
, DR
c
, DQ
c
), haplotype d (A
d
, B
d
, C
d
, DR
d
, DQ
d
), haplotype g (A
g
, B
g
, C
g
, DR
g
, DQ
g
), haplotype h (A
h
, B
h
, C
h
, DR
h
, DQ
h
), or haplotype j (A
j
, B
j
, C
j
, DR
j
, DQ
j
).
In preferred embodiments, the swine is capable of reproduction, i.e., the animal can produce functional gametes.
In another aspect, the invention features, a cell or a preparation of such cells, from a swine, preferably a miniature swine, which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
In preferred embodiments, the swine cell is an embryonic stem cell. In other preferred embodiments, the swine cell can be a hematopoietic stem cell, e.g., a cord blood hematopoietic stem cell, a bone marrow hematopoietic stem cell, or a fetal or neonatal liver or spleen hematopoietic stem cell; a differentiated blood cell, e.g., a myeloid cell, a megakaryocyte, a monocyte, a granulocyte, an eosinophil, an erythroid cell, a lymphoid cell, such as a B e o lymphocyte or a T lymphocyte; a pluripotent hematopoietic stem cell, e.g., a hematopoietic precursor, a burst-forming units-erythroid (BFU-E), a colony forming unit-erythroid (CFU-E), a colony forming unit-megakaryocyte (CFU-Meg), a colony forming unit-granulocyte-monocyte (CFU-GM), a colony forming unit-eosinophil (CFU-Eo), or a colony forming unit-granulocyte-erythrocyte-megakaryocyte-monocyte (CFU-GEMM); a swine cell other than a hematopoietic stem cell or other blood cell; a swine thymic cell, e.g., a swine thymic stromal cell; a bone marrow stromal cell; a swine liver cell; a swine kidney cell; a swine epithelial cell; a swine muscle cell, e.g., a heart cell; or a dendritic cell or precursor thereof.
In preferred embodiments, at least 65%, 70%, 75%, 80%, 85%, 90%, 95% or more, of all other genetic loci in the swine cell are homozygous.
In preferred embodiments, the swine leukocyte antigens (SLA) A, B, C, DR, and DQ can be of haplotype a (A
a
, B
a
, C
a
, DR
a
, DQ
a
), haplotype c (A
c
, B
c
, C
c
, DR
c
, DQ
c
), haplotype d (A
d
, B
d
, C
d
, DR
d
, DQ
d
), haplotype g (A
g
, B
g
, C
g
, DR
g
, DQ
g
), haplotype h (A
h
, B
h
, C
h
, DR
h
, DQ
h
), or haplotype j (A
j
, B
j
, C
j
, DR
j
, DQ
j
).
In another aspect, the invention features, an isolated cell nucleus from a swine cell, preferably a miniature swine cell, which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous. In preferred embodiments, the cell nucleus is from an undifferentiated cell. In other embodiments, the cell nucleus is from a differentiated cell.
In preferred embodiments, at least 65%, 70%, 75%, 80%, 85%, 90%, 95% or more, of all other genetic loci in the swine cell nucleus are homozygous.
In preferred embodiments, the swine leukocyte antigens (SLA) A, B, C, DR, and DQ can be of haplotype a (A
a
, B
a
, C
a
, DR
a
, DQ
a
), haplotype c (A
c
, B
c
, C
c
, DR
c
, DQ
c
), haplotype d (A
d
, B
d
, C
d
, DR
d
, DQ
d
), haplotype g (A
g
, B
g
, C
g
, DR
g
, DQ
g
), haplotype h (A
h
, B
h
, C
h
, DR
h
, DQ
h
), or haplotype j (A
j
, B
j
, C
j
, DR
j
, DQ
j
).
In another aspect, the invention features, an isolated organ, or a tissue, from a swine, preferably a miniature swine, which swine is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
In preferred embodiments, the organ can be an organ of the gastrointestinal tract, a liver, a kidney, a pancreas, a stomach, a spleen, or a gallbladder; a sensory organ, e.g., an eye; a lung; on organ or tissue of the circulatory system, e.g., a heart. In other preferred embodiments, the tissue can be connective tissue; epithelial tissue, e.g., skin; muscle tissue; osseous tissue; vascular tissue, e.g., a blood vessel; or occular tissue, e.g., lens tissue.
In preferred embodiments, the isolated organ or tissue is from a postnatal animal, e.g., a juvenile or adult animal, or a prenatal animal, e.g., a fetus or an embryo.
In preferred embodiments, at least 65%, 70%, 75%, 80%, 85%, 90%, 95% or more, of all other genetic loci in the swine are homozygous.
In preferred embodiments, the swine leukocyte antigens (SLA) A, B, C, DR, and DQ can be of haplotype a (A
a
, B
a
, C
a
, DR
a
, DQ
a
), haplotype c (A
c
, B
c
, C
c
, DR
c
, DQ
c
), haplotype d (A
d
, B
d
, C
d
, DR
d
, DQ
d
), haplotype g (A
g
, B
g
, C
g
, DR
g
, DQ
g
), haplotype h (A
h
, B
h
, C
h
, DR
h
, DQ
h
),

Affiliated with

Also associated with

Rating

Inbred miniature swine and uses thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inbred miniature swine and uses thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inbred miniature swine and uses thereof will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2993253