BALB/c mice homozygous for the bpk gene exhibit a form of autosomal recessive (AR)
polycystic kidney disease (PKD) with massive collecting duct
cysts, common bile duct dilation and chaotic intrahepatic bile ducts/portal triads. The combined renal and biliary pathology mimics much of the pathology seen in human
ARPKD. Murine models of
ARPKD generally have a reduced renal expression of
epidermal growth factor (
EGF) and an increased expression of
EGF receptors (
EGF-R). However, the role that
EGF and
EGF-R play in the progression of PKD has been unclear. Evidence from various model systems/ages of treatment produces conflicting results. Treating neonatal C57BL/6J-cpk mice with
EGF ameliorates the renal pathology and dysfunction while treating 2- and 3-week-old bpk mice with an
EGF-receptor tyrosine kinase inhibitor also ameliorates
ARPKD. Therefore, to determine whether neonatal
EGF treatment would accelerate or inhibit the progression of the PKD in bpk mice, we administered exogenous
EGF (1 microgram/g
body weight subcutaneously) daily from postnatal days 3-9 (a critical period for tubule maturation). Neonatal
EGF treatment but not
sham treatment retarded the development of
azotemia and common bile duct dilation and the chaotic hepatic triad changes in cystic mice. However,
EGF treatment neither reduced the severity of the renal cystic pathology nor reduced the degree of cystic enlargement of the kidneys. Cystic mice treated past 9 days of age died prior to their scheduled termination at 21 days of age. The role of
EGF in the progression of
polycystic kidney disease in bpk mice is relatively complicated, with neonatal treatment being associated with some amelioration of the renal dysfunction and extrarenal pathology without an effect on the renal pathology. Continuation of treatment beyond 9 days increased morbidity. Therefore, in discussing the role of
EGF or
EGF receptor in mediating the pathophysiology of PKD, the stage of development may be an important consideration.