450 
HEMATOLOGY 
Substances in serum. 
Gene 
Substances in saliva* 
acquired by 
combinations 
red blood cells 
0 
R 
0 
R 
I/-R/- 
+ 
+ 
+ 
l/-rOrO 
+ 
+ 
ii 
* As indicated by inhibition tests. 
Figure 1. — Genotypes and phenotypes in the R-0 
system" 
anti-R sera are often variable in their reaction 
with R erythrocytes. For this reason most 
screening for the R antigen is done with bovine 
anti-J antiserum which cross-reacts well and is 
not as variable in its reactions with the sheep 
R-antigen. 
The erythrocytes of newborn lambs are R- 
negative and 0-negative. However, depending 
upon the lamb's genetic complement, soluble R 
or 0 substance can be detected in the serum by 
inhibition tests. Studies by RendeP have shown 
that the erythrocytes of newborn lambs with R 
substance in their serum became R-positive in 
an average of 16.4 days after birth and that 
lambs with detectable 0 substance show 0 posi- 
tive erythrocytes in an average of 28.4 days 
after birth. Anti-R is not detectable in the 
serum of newborn lambs before suckling. It is 
detectable in group 0 lambs during suckling if 
the dam is group 0. However, these passively 
acquired antibodies disappear at from 10 to 26 
days of age, and no actively produced anti-R is 
detectable before the lamb is 5 to 7 months of 
age. 
In R positive adult sheep the plasma contains 
soluble R substance and the plasma of 0 posi- 
tive sheep contains soluble 0 substance. In 
group R sheep, R substance is not only detect- 
able in the erythrocytes and in the serum, it has 
also been demonstrated in the milk, saliva, and 
seminal fluid. 0 substance has been detected in 
the milk, plasma and semial fluid of group O 
sheep, and also in the seminal fluid and plasma 
of group R sheep. Neither substance has been 
detected in significant amounts in the body 
fluids of group i sheep. RendeP has postulated 
that the I gene functions in a capacity similar 
to the secretor gene in man who secretes Le*" 
substance in his saliva. Rendel et al.'^ have 
shown that group 0 erythrocytes incubated in 
serum from a group R sheep became R positive 
and can be lysed by both anti-R and anti-0 sera. 
Likewise, group i erythrocytes became O posi- 
tive when incubated with serum from group 0 
sheep. Thus the R and 0 antigens are appar- 
ently produced by cells outside of the hemato- 
poietic system and are acquired as a coating 
substance by the sheep erythrocytes. 
The R and 0 antigens of sheep have been 
demonstrated to be serologically related to eryth- 
rocyte antigens in other species. For example, 
Amzel et al.'-* have shown a serologic relation- 
ship between R of sheep and A of man. 
Neimann-Sorensen et al.^" have studied the sero- 
logic relationship of A of man, R of sheep and J 
of cattle. The 0 substance of sheep is related to 
the H substance of man : saliva from human se- 
cretors inhibits the 0 anti-sheep 0 reaction 
while saliva from human non-secretors does 
not.io 
The X-Z system was the second major blood 
group discovered in sheep. It is a two allele sys- 
tem with three recognized phenotypes: X, XZ, 
and Z. It was first described by Rasmusen^^ 
using as a reagent heteroimmune antisera per- 
pared by immunization of rabbits with sheep 
red cells. The heteroimmune antiserum lysed 
X-positive sheep erythrocytes in the presence of 
rabbit or guinea pig complement. When solu- 
tions of anti-X antiserum were adsorbed with 
sheep erythrocytes from ten individuals, it was 
noted that the erythrocytes from one individual 
failed to adsorb all hemolysins. When the red 
cells of the nine individuals which has shown 
complete adsorption were incubated in the pres- 
ence of complement in the single solution where 
adsorption was incomplete, lysis occurred in 
seven cases, but the erythrocytes of two individ- 
uals remained unlysed. This was interpreted as 
evidence that genetic dosage was involved in the 
reactions. The hemolysins remaining in the so- 
lution where adsorption was incomplete might 
be in sufficient quantity to lyse red cells from 
sheep homozygous for factor X but not to lyse 
cells from sheep heterozygous for factor X. The 
search for a complementary blood factor Z was 
begun. Anti-Z antiserum was first prepared by 
