Phenotypes Associated with This Genotype

Genotype
MGI:2669229

• Allelic Composition: Prox1^tm1Gco/Prox1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * NMRI

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality, incomplete penetrance ( J:53431 , J:102652 )

• Background Sensitivity: unlike on other backgrounds, 1 of 30 heterozygotes survive (J:53431)

respiratory system

chylothorax ( J:102652 )

• heterozygotes that die within a few days of birth have milky chylous ascites in the peritoneal cavity and/or thoracic cavity

respiratory distress ( J:102652 )

• heterozygotes that die without suckling are in respiratory distress

digestive/alimentary system

abnormal intestine morphology ( J:102652 )

• accumulation of lipid is seen in the intestine walls of heterozygotes that die postnatally

immune system

abnormal lymph circulation ( J:57646 , J:102652 )

• 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)

increased macrophage cell number ( J:102652 )

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

abnormal lymphatic vessel morphology ( J:102652 )

• 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

increased inflammatory response ( J:102652 )

• inflammation of the mesothelial membrane in obese adults

homeostasis/metabolism

increased circulating glucagon level ( J:102652 )

• after the onset of obesity serum glucagon is increased

increased circulating insulin level ( J:102652 )

• after the onset of obesity serum insulin is increased; however serum glucose levels are similar to wild-type

increased circulating leptin level ( J:102652 )

• serum leptin is increased after the onset of obesity but not before

increased circulating alanine transaminase level ( J:102652 )

• the serum ratio of alanine aminotransferase to aspartate aminotransferase is elevated in obese mice

cyanosis ( J:102652 )

• heterozygotes that die without suckling appear cyanotic

edema ( J:57646 , J:102652 )

• 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)

chylothorax ( J:102652 )

• heterozygotes that die within a few days of birth have milky chylous ascites in the peritoneal cavity and/or thoracic cavity

increased liver triglyceride level ( J:102652 )

• triglyceride accumulation is seen in the liver in obese mice

vision/eye

abnormal eye development ( J:83185 )

• after 10 days in culture heterozygous retinal explants have about more cells compared to wild-type explants but fewer than in homozygous explants

abnormal retina morphology ( J:83185 )

• severe retinal dysplasia is seen in older mice degeneration is seen in all 3 retinal layers

increased total retina thickness ( J:83185 )

• in adults the retina is thicker than in wild-type mice

growth/size/body

increased susceptibility to age related obesity ( J:102652 )

• 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

increased total body fat amount ( J:102652 )

• weight gain is associated with accumulation of the subcutaneous and intra-abdominal fat

increased fat cell size ( J:102652 )

• adipocyte hypertrophy and, in 2 of the most obese mice, hyperplasia are seen

increased total fat pad weight ( J:102652 )

• 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

abnormal suckling behavior ( J:102652 )

• many heterozygotes die without suckling

decreased locomotor activity ( J:102652 )

• 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

increased liver triglyceride level ( J:102652 )

• triglyceride accumulation is seen in the liver in obese mice

hepatic steatosis ( J:102652 )

• 4 of 6 obese mice have fatty livers but no lean mice have fatty livers

hematopoietic system

increased macrophage cell number ( J:102652 )

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

cardiovascular system

abnormal lymph circulation ( J:57646 , J:102652 )

• 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		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:102652