Identification of (CAG)(n) and (CGG)(n) repeat-binding proteins, CAGERs expressed in mature neurons of the mouse brain

The trinucleotide repeats (CAG)(n) and (GGG)(n) have been shown to be expan ded in responsible genes of several human hereditary neurological disorders . In studies of mice, we previously identified two homologous single-strand ed (ss)(CAG) and ss(CGG) repeat-binding proteins, CAGER-1 (44 kDa) and CAGE R-2 (40 kDa) (CAG-element-recognizing proteins). The specific binding activ ities of these proteins were predominantly detected in the mouse brain. We have isolated the cDNAs encoding CAGER-1 and CAGER-2 and found that they we re identical to previously reported cDNAs for Pur alpha and Pur beta, respe ctively. Pur alpha of 28 kDa was previously identified as a replication-ori gin-binding protein that is ubiquitously expressed in proliferating cells. We show that the transcripts of CAGERs increase after birth and are detecte d at high levels in the adult mouse brain but at very low or virtually unde tectable levels in other mouse tissues. Biochemical properties and molecula r weights are different between CAGERs and Pur alpha/beta. Immunostaining w ith specific antibodies against CAGERs indicates that CAGERs in the mouse b rain reside in nonproliferating neurons but not in proliferating glia. We c onclude that CAGERs and Pur alpha/beta are unrelated proteins, and CAGERs a re neuronal single-stranded sequence-binding proteins in the mouse brain. M isassignment of cDNAs is described. (C) 1999 Academic Press.