Redesigning Animal Agriculture

106 D.N. Wells and G. Laible
major osmotic regulator of milk secretion
and is synthesized by the lactose synthetase
complex. This complex comprises two
enzymes, one of which is the milk protein αlactalbumin.
The disruption of both copies
of the α-lactalbumin gene in mice resulted
in lactose-free milk, but strongly affected
the osmotic regulation of milk, resulting in
the production of a highly viscous secretion
incapable of supporting adequate nutrition
in suckling young (Stinnakre et al., 1994).
In the heterozygous state, with one inactive
α-lactalbumin allele, milk had a modest
10–20% decrease in lactose content and a
similar percentage increase in the concentration
of total milk solids. An alternative
approach of expressing a lactose hydrolysing
enzyme in the mammary gland under
the control of the α-lactalbumin promoter
was more successful (Jost et al., 1999). In
heterozygous females, lactose was still produced
and subsequently hydrolysed into
the osmotically active monosaccharides
glucose and galactose. Overall, milk lactose
was reduced by 50–85% and there was only
a slight increase in osmolarity. If extended
to bovine milk, such a reduction in lactose
could possibly ameliorate lactose intolerance
(Jost et al., 1999). Moreover, there was
no apparent change in either fat or protein
concentration and the milk successfully
nourished offspring. Whilst the results from
these transgenic mouse studies are promising,
given the intrinsic differences in milk
composition between mice and cows, the
success of such a transgenic approach can
only be assessed when applied to dairy cattle.
Furthermore, the functional properties
of any altered milk need to be evaluated to
determine its suitability for processing into
a range of dairy products. Aside from the
issue of lactose intolerance, an acceptable
reduction in lactose would be beneficial in
concentrating milk solids, provided it did
not compromise milk let-down, and lower
the transportation costs of liquid milk from
the farm to the dairy factory. This might be
achieved by controlled regulation of lactase
expression, α-lactalbumin gene dosage or
RNAi knockdown.
Milk fat is very rich in saturated fatty
acids, which have been associated with
cardiovascular and coronary heart disease.
The fatty acid composition of milk could
be improved by modulating the enzymes
involved in de novo lipid metabolism to
decrease the unhealthy fats in favour of
unsaturated fats (Wall et al., 1997). However,
manipulation of unsaturated fatty acid composition
in milk may be more effectively
achieved by varying the diet of the dairy
cows, through the use of particular forage
species or feed additives (Palmquist et al.,
1993) and has been a successful approach
to produce spreadable butter (Fearon et al.,
2004).
Consideration has also been given to
reducing the total fat content of milk (Wall
et al., 1997). Milk typically contains around
3.8% fat, 50% of which is synthesized in the
mammary gland and is thus energe tically
expensive for the cow to make. If a strategy
was used to knockdown the expression of
acetyl-coenzyme A carboxylase in the mammary
gland, for instance, de novo fatty acid
synthesis might be reduced, resulting in a
natural low-fat liquid milk desired by consumers
(Wall et al., 1997). This approach
could also reduce the feed energy requirements
for the cow, lowering the cost of milk
production. It could also reduce the mobilization
of adipose tissue during early lactation
and likely improve conception rates to
maintain a 365-day calving interval, important
in many seasonal pastoral dairy farming
systems.
Considering the importance of milk
protein for the quality and yield of dairy
products, there is strong interest by both
farmers and milk processors to improve
milk protein content. Cheese, for example,
is essentially composed of casein, which
accounts for about 80% of total milk protein,
and milk fat. Any increase in the casein
content is therefore an improvement for the
manufacture of cheese. Moreover, the casein
fractions, comprising four different casein
proteins and numerous variants, are aggregated
into large colloidal micelles which are
a major determinant of the physico chemical
properties of milk. One casein protein in
particular, κ-casein, occupies the surface
of the micelle and influences the size of
this protein particle. This has been demon-