Caprine beta-D-mannosidosis: characterization of a model lysosomal storage disorder.

Interest in using caprine beta-D-mannosidosis as a model to evaluate bone marrow transplantation in the treatment of human lysosomal storage disorders provided the stimulus for characterization of beta-D-mannosidase in selected goat tissues and induction of hemopoietic chimerism in the goat. Total beta-D-mannosidase activity was measured with the use of 4-methylumbelliferyl beta-D-mannopyranoside as substrate. Residual activity in mutant liver was 52% of control but no activity was detectable in mutant kidney or brain tissue. Normal adult goat liver contained two forms of beta-D-mannosidase, a nonlysosomal form (52%) with a broad pH range for optimum activity (4.5-8.0) and a lysosomal form (48%) with a pH optimum of 5.5. Residual enzyme in mutant liver consisted entirely of the nonlysosomal form. Normal adult thyroid, kidney and brain contained two major lysosomal isoenzymes with pIs 5.5 and 5.9 and traces of a minor isoenzyme with pI 5.0. Normal liver contained three isoenzymes with similar pIs; however, an isoenzyme with pI 5.0 predominated. In 60-day fetal liver lysosomal isoenzymes predominated and only trace amounts of nonlysosomal isoenzyme were detectable. Total hepatic beta-D-mannosidase activity increased towards adult levels during the last 90 days of gestation as a result of increasing nonlysosomal isoenzyme activity. Intraperitoneal injection of fetal liver cells into 60-day goat fetuses resulted in sustained hemopoietic chimerism in surviving kids without evidence of graft-versus-host-disease. These results suggest that transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with beta-D-mannosidosis is feasible and may provide an alternative strategy for evaluation of postnatal bone marrow transplantation in the treatment of human lysosomal storage disorders.

A 14/20 chromosome translocationp in Simmental cattle.

A 14/20 translocation was identified in 2 herds of Simmental cattle in the United States. All of the animals that carried the translocation had a common sire that was identified subsequently to carry the translocation. The semen of the bull had been used to inseminate a vast number of cows, so a substantial number of Simmental cattle in the United States may carry the 14/20 translocation. This translocation could have a detrimental effect on fertility in carrier animals; however, there are insufficient data about this particular abnormality to form conclusions. There appears to be sufficient evidence to urge caution in selecting carriers for breeding stock, especially when the potential exists for widespread dissemination of the abnormality through the use of artificial insemination.

Establishment of pregnancy after embryo transfer in mares with gonadal dysgenesis.

Embryo transfer was performed in three mares with gonadal dysgenesis. Karyotypes of the mares were as follows: Mare 1, 63,XX, 64,XX, 65,XX; Mare 2, 63,X; and Mare 3, 65,XXX. The mares were administered progesterone in oil, 300 mg intramuscularly daily, starting 1 or 2 days after donor mare ovulation. Embryos were transferred on day 7 after donor ovulation. Mare 1 became pregnant after the first embryo transfer and had a normally developing fetus on necropsy on day 45 of gestation. Mare 3 became pregnant after the third embryo transfer, but the embryo was lost between day 14 and day 18 of gestation. Mare 2 received embryos on six occasions without maintaining pregnancy after transfer. Mares with gonadal dysgenesis treated with progesterone can establish and maintain pregnancy after embryo transfer, but there may be differences in this capability among mares, possibly related to the cause of the gonadal dysgenesis.

Standard karyotype of the domestic horse (Equus caballus). Committee for standardized karyotype of Equus caballus. The Second International Conference for Standardization of Domestic Animal Karyotypes, INRA, Jouy-en Josas, France, 22nd-26th May 1989.

The following decisions concerning the banded karyotype of the horse (Equus caballus) were made at the second International conference for Standardization of Domestic Animal Karyotypes, held at Jouy-en Josas, France, 22nd-26th May 1989: (1) numbering of the chromosomes was modified to correspond to an arrangement into only two groups (the non-acrocentrics and the acrocentrics) within which the autosomes are placed according to length alone; (2) a more compact karyotype arrangement was adopted: chromosomes 1 to 5 on the first row, 6 to 10 on the second, 11 to 13, and, at the far right, X and Y on the third row, 14 to 19 on the fourth row, chromosomes 20 to 25 on the fifth, and 26 to 31 on the sixth row; (3) the NOR-bearing horse chromosomes were identified as numbers 1, 28 and 31.

Induction of hemopoietic chimerism in the caprine fetus by intraperitoneal injection of fetal liver cells.

Intraperitoneal injection of allogeneic liver cells from 43-day-old male fetuses into normal 60-day female goat fetuses resulted in persistent hemopoietic chimerism in surviving recipients without clinical evidence of graft-versus-host disease. Transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with beta-D-mannosidosis may provide an alternative strategy for evaluating hemopoietic stem cell transplantation in the treatment of human lysosomal storage diseases.