The C3H/HeJ inbred mouse is a model of vesico-ureteric reflux with a susceptibility locus on chromosome 12.
Vesico-ureteric reflux is the most common congenital anomaly of the urinary tract, characterized by a defective uretero-vesical junction with retrograde urine flow from the bladder toward the kidneys. Because there is strong evidence for a genetic basis for some cases of vesico-ureteric reflux, we screened 11 inbred mouse strains for reflux and kidney size and identified one strain, C3H/HeJ, that has a 100 percent incidence of vesico-ureteric reflux with otherwise normal kidneys at birth. These mice are predisposed to reflux as a result of a defective uretero-vesical junction characterized by a short intravesical ureter. This defect results from a delay in urinary tract development initially manifested by a ureteric bud arising from a more caudal location along the mesonephric duct. In contrast, C57BL/6J mice (resistant to reflux at birth) have long intravesical ureters, normally positioned ureteric buds, and no delay in urinary tract development. Genome-wide and additional fine mapping of backcross mice, derived from C3H/HeJ and C57BL/6J crosses, identified a significant reflux susceptibility locus, Vurm1, on chromosome 12 (peak logarithm of the odds=7.39). The C3H/HeJ mouse is a model of vesico-ureteric reflux without renal malformation, and further characterization of this model will allow for the identification of a pathway important for urinary tract development, a finding that will serve as a model for the human disorder.
Murawski
Inga J
IJ
Department of Pediatrics, McGill University, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Maina
Rita W
RW
Malo
Danielle
D
Guay-Woodford
Lisa M
LM
Gros
Philippe
P
Fujiwara
Mary
M
Morgan
Kenneth
K
Gupta
Indra R
IR
D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020161:Physical Chromosome Mapping; D014513:Ureter / Q000002:abnormalities; D001743:Urinary Bladder / Q000002:abnormalities; D014551:Urinary Tract / Q000002:abnormalities / Q000196:embryology; D014718:Vesico-Ureteral Reflux / Q000196:embryology / Q000235:genetics*