Malaria parasites undergo a sporogonic cycle in the mosquito vector, S
porozoites, the form of the parasite injected into the host during a b
loodmeal, develop inside oocysts in the insect midgut, then migrate to
and eventually invade the salivary glands, The circumsporozoite prote
in (CS), one of the major proteins synthesized by salivary gland sporo
zoites', is a surface-associated molecule which is important in sporoz
oite infectivity to the host(2). Here, by gene targeting, we created P
lasmodium berghei lines in which the single-copy CS gene was disrupted
, The CS(-) and wild-type parasites produced similar numbers of oocyst
s of comparable size in the mosquito midgut, In the CS(-) oocysts, how
ever, sporozoite formation was profoundly inhibited. CS therefore appe
ars to have a pleiotropic role and to be vital for malaria parasites i
n both the vector and the host: in mosquitoes, CS is essential for spo
rozoite development within oocysts, and in the vertebrate host it prom
otes sporozoite attachment to hepatocytes(3-7).