Mouse Genome Informatics
ht
    Prox1tm1Gco/Prox1+
involves: 129S1/Sv * 129X1/SvJ * NMRI
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• Background Sensitivity: unlike on other backgrounds, 1 of 30 heterozygotes survive (J:53431)

respiratory system
• heterozygotes that die within a few days of birth have milky chylous ascites in the peritoneal cavity and/or thoracic cavity
• heterozygotes that die without suckling are in respiratory distress

digestive/alimentary system
• accumulation of lipid is seen in the intestine walls of heterozygotes that die postnatally

immune system
• the intestines are filled with a white fluid (probably chyle) a few hours before death (J:57646)
• leakage of chyle from the mesenteric vessels (J:102652)
• dye injected into the dermal lymph vessels surrounding the popliteal and inguinal lymph nodes abnormally accumulates in the cutaneous lymphatics between the injection site and the draining lymph nodes (J:102652)
• dye injected into the foot pad accumulates in multiple hypoplastic and tortuous lymphatic vessels in the thoracic cavity rather than in the thoracic duct (J:102652)
• an increase number of Mac-2+ macrophages is seen along with liver lipid accumulation
• lymph vessels are mispatterned and dilated, with those in the intestine and mesentery most severely affected
• vessels sprout from the mesenteric lymphatics and invade the mesothelial membrane which does not normally contain lymph vessels
• some endothelial cells lining intestinal lymph ducts are discontinuous and ruptured
• inflammation of the mesothelial membrane in obese adults

homeostasis/metabolism
• after the onset of obesity serum glucagon is increased
• after the onset of obesity serum insulin is increased; however serum glucose levels are similar to wild-type
• serum leptin is increased after the onset of obesity but not before
• the serum ratio of alanine aminotransferase to aspartate aminotransferase is elevated in obese mice
• heterozygotes that die without suckling appear cyanotic
• severe edema develops around E14.5 (J:57646)
• at E14.5 and at E16.5 all heterozygous embryos have edema; however edema is resolved before birth (J:102652)
• some heterozygotes in respiratory distress had clear fluid accumulation in the thoracic cavity (J:102652)
• heterozygotes that die within a few days of birth have milky chylous ascites in the peritoneal cavity and/or thoracic cavity
• triglyceride accumulation is seen in the liver in obese mice

vision/eye
• after 10 days in culture heterozygous retinal explants have about more cells compared to wild-type explants but fewer than in homozygous explants
• severe retinal dysplasia is seen in older mice degeneration is seen in all 3 retinal layers
• in adults the retina is thicker than in wild-type mice

growth/size
• weight gain is associated with accumulation of the subcutaneous and intra-abdominal fat
• the average weight of 6- to 12-month old heterozygotes is 67.9g compared to 51.8g for wild-type mice
• the most marked weight gain is seen between 9 weeks and 6 months of age

adipose tissue
• weight gain is associated with accumulation of the subcutaneous and intra-abdominal fat
• adipocyte hypertrophy and, in 2 of the most obese mice, hyperplasia are seen
• fat accumulation is most obvious in fat pads around lymph nodes
• individual fat pads in older heterozygotes weigh 2 to 3 times more than wild-type

behavior/neurological
• many heterozygotes die without suckling
• after the onset of obesity, heterozygotes exercise much less than wild-type mice and tend to eat less; however before the onset of obesity no difference in food consumption or activity is seen

liver/biliary system
• triglyceride accumulation is seen in the liver in obese mice
• 4 of 6 obese mice have fatty livers but no lean mice have fatty livers

hematopoietic system
• an increase number of Mac-2+ macrophages is seen along with liver lipid accumulation

cardiovascular system
• the intestines are filled with a white fluid (probably chyle) a few hours before death (J:57646)
• leakage of chyle from the mesenteric vessels (J:102652)
• dye injected into the dermal lymph vessels surrounding the popliteal and inguinal lymph nodes abnormally accumulates in the cutaneous lymphatics between the injection site and the draining lymph nodes (J:102652)
• dye injected into the foot pad accumulates in multiple hypoplastic and tortuous lymphatic vessels in the thoracic cavity rather than in the thoracic duct (J:102652)

Mouse Models of Human Disease
OMIM IDRef(s)
Lymphangiectasia, Pulmonary, Congenital; CPL 265300 J:102652
Obesity 601665 J:102652