We investigated the phenotype of Anx-A1-/- mice and studied the appearance of the gene expression during embryonic and postnatal development. Anx-A1-/- mice are fertile and there were no apparent differences in litter sizes or other breeding statistics when compared to litter mate Anx-A1+/+ controls. The null mice grew at the same rate as the Anx-A1+/+ controls and appeared normal at all ages. Plasma sodium, potassium and possibly calcium were slightly elevated in an apparently genotype-dependent fashion, although all these differences were probably still within the normal range. The liver enzyme ALT was significantly elevated in the Anx-A1-/- mice but most other aspects of blood chemistry were no different. In terms of post mortem pathology, there were few exceptional findings although genotype related changes were seen in the weight of the liver, heart, thymus, pancreas, pituitary gland and kidney at necroscopy. Examination by western blotting of the tissue concentrations of other members of the annexin family revealed that Anx-A1 gene deletion lead, in some organs (e.g. lung and thymus), to changes in the tissue concentration of other annexins as well as the pro-inflammatory enzymes COX-2, cPLA2 and iNOS. There was some evidence of a sexual dimorphism in this effect. Anx-A1 gene expression was first detected at embryonic day 10.5 in the corneal epithelium. Thereafter, the skin, bone and respiratory tract were among several sites that displayed strong gene expression during embryonic development whereas the brain and the heart exhibited little gene expression at any developmental stage. These findings are discussed in relation to several proposed roles for the protein.
|Original language||American English|
|State||Published - 2004|