ALTERED IGFBP5 GENE-EXPRESSION IN THE CEREBELLAR EXTERNAL GERMINAL LAYER OF WEAVER MUTANT MICE

The IGF system components play important roles in cerebellar developme nt as demonstrated by their specific spatial-temporal expression. IGF- I, type I IGF receptor (IGFR-I), IGFBP2 and IGFBP5 mRNA are localized in distinct cell populations, and all are expressed at the highest lev els at the peak of Purkinje cell growth, active synaptogenesis and den dritic formation. To understand IGF-I's action at the cellular level, in situ hybridization was employed to investigate the distribution of IGF system gene transcripts in the cerebellum of weaver mutant mice (w v/wv). Although located ectopically, the surviving Purkinje cells expr ess IGF-I mRNA at the same level in wv/wv as in +/+. No alteration in the cellular distribution or mRNA levels was observed with IGFBP2, or IGFR-I mRNAs. However, the pattern of IGFBP5 expression is altered in the external germinal layer of wv/wv mice. Not only is IGFBP5 expresse d by more granule cell precursors of wv/wv cerebellum, but its mRNA le vel is 2.3 fold that of +/+. The altered IGFBP5 gene expression in gra nule cell precursors may modulate the interaction of IGF-I with IGFR-I in ways that contribute to their massive death occurring in the devel opment of wv/wv cerebellum.