Expression of enhancing factor/phospholipase A(2) in ICRC mice

Enhancing factor (EF), a growth factor modulator, recently identified as th e mouse secretory phospholipase A(2) (PLA(2)), has been isolated in our lab oratory from the intestines of mice. EF modulates the action of epidermal g rowth factor (EGF) by mediating an almost 2-fold increase in EGF binding in a radioreceptor assay. EF has been localized immunohistochemically to the Paneth cells of the intestine, adjacent to the proliferating stem cell popu lation. Although very weak staining was observed in the intestines of ICRC mice (ICRC is an inbred strain of mouse developed at this Institute) as com pared to Balb/c. mice, the enhancing activity was not detected in the parti ally purified, acid soluble intestinal proteins of the ICRC strain. However , studies using polyclonal antibodies against purified EF demonstrated that EF from Balb/c and ICRC intestines are either immunologically identical or closely related to each other although, quantitatively, EF was very low in ICRC mice. RFLP studies indicated that ICRC mice carry a mutation in the c oding region of the EF gene resulting in loss of the BamHI restriction site . On sequencing, a T insertion was found at position 166 from the ATG site thereby causing a disruption in the ORF. This probably results in undetecta ble levels of enhancing activity. In this paper we report the molecular cha racterization of the ICRC mouse with respect to the enhancing factor gene.