Phenotypes associated with this allele

• Allele Symbol: Prox1^tm2Gco
• Allele Name: targeted mutation 2, Guillermo Oliver
• Allele ID: MGI:3609548
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Prox1^tm2Gco/Prox1^tm2Gco Myf5^tm3(cre)Sor/Myf5^+	involves: 129S1/Sv * 129S4/SvJae * C57BL/6J	MGI:5907124
cn2	Prox1^tm2Gco/Prox1^tm2Gco Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:5907122
cn3	Prox1^tm1Gco/Prox1^tm2Gco Tg(Tek-cre)1Ywa/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3759503
cn4	Prox1^tm2Gco/Prox1^+ Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * C57BL/6 * NMRI * SJL	MGI:3611343

Genotype
MGI:5907124

cn1

• Allelic Composition: Prox1^tm2Gco/Prox1^tm2Gco; Myf5^tm3(cre)Sor/Myf5⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6J

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

muscle

abnormal skeletal muscle morphology ( J:212185 )

• mice exhibit a switch from a slow- to fast-twitch skeletal muscle phenotype, with an elevation of fast-twitch skeletal muscle gene expression in gastrocnemius and soleus muscles, a decrease in the type I fibers and increase in type IIa fibers in the soleus muscle, and an increase in maximal (tetanic) contractile strength and decrease in half relaxation time in the soleus

• however, no changes in the overall oxidative capacity of mutant soleus or EDL muscles and hearts do not exhibit myofibril disarray

Genotype
MGI:5907122

cn2

• Allelic Composition: Prox1^tm2Gco/Prox1^tm2Gco; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

growth/size/body

enlarged heart ( J:212185 )

• cardiomegaly at 12 weeks of age

mortality/aging

premature death ( J:212185 )

• in mice that survive postnatally, lethality becomes fully penetrant between 7 and 14 weeks

postnatal lethality, incomplete penetrance ( J:212185 )

• about half the expected number of mutants are seen at P10

cardiovascular system

abnormal heart morphology ( J:212185 )

• fast-twitch skeletal muscle gene expression is elevated in hearts

abnormal myocardial fiber morphology ( J:212185 )

• myofibrillar disarray

thin myocardium ( J:212185 )

• myocardial thinning at late stages

thick tricuspid valve cusps ( J:212185 )

• thickening of the tricuspid valve leaflets

abnormal interventricular septum morphology ( J:212185 )

• mild ventricular septal defects

interventricular septum membranous part aneurysm ( J:212185 )

• the membranous portion of the ventricular septum is aneurysmal

abnormal interventricular septum muscular part morphology ( J:212185 )

• 20% of hearts show imperfections in the muscular ventricular septum

enlarged heart ( J:212185 )

• cardiomegaly at 12 weeks of age

dilated heart ( J:212185 )

• chamber dilation in both the atria and ventricles, with severity of dilation increasing with age to eventually affect all cardiac chambers

dilated cardiomyopathy ( J:212185 )

• between 8 and 14 weeks of age, all hearts are characterized by cardiac enlargement, chamber dilation, ventricular wall thinning, cardiac stress marker activation, and systolic dysfunction

• however, no obvious concentric cardiomyocyte hypertrophy is seen

decreased heart ventricle muscle contractility ( J:212185 )

• dilated and poorly contracting ventricles at 6 weeks of age, with mean left ventricular ejection fraction less than 30%

homeostasis/metabolism

abnormal cardiac thrombosis ( J:212185 )

• mice develop large intra-atrial and intraventricular thrombi at 12 weeks of age, indicating hemostasis associated with poor systolic function

• thrombi are seen as early as 8 weeks of age

abnormal atrial thrombosis ( J:212185 )

• large intra-atrial thrombi at 12 weeks of age

abnormal ventricular thrombosis ( J:212185 )

• large intraventricular thrombi at 12 weeks of age

muscle

abnormal myocardial fiber morphology ( J:212185 )

• myofibrillar disarray

thin myocardium ( J:212185 )

• myocardial thinning at late stages

dilated cardiomyopathy ( J:212185 )

• between 8 and 14 weeks of age, all hearts are characterized by cardiac enlargement, chamber dilation, ventricular wall thinning, cardiac stress marker activation, and systolic dysfunction

• however, no obvious concentric cardiomyocyte hypertrophy is seen

decreased heart ventricle muscle contractility ( J:212185 )

• dilated and poorly contracting ventricles at 6 weeks of age, with mean left ventricular ejection fraction less than 30%

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:212185

Genotype
MGI:3759503

cn3

• Allelic Composition: Prox1^tm1Gco/Prox1^tm2Gco; Tg(Tek-cre)1Ywa/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

immune system

absent lymphatic vessels ( J:125507 )

• no deep lymphatic vessels are observed

Genotype
MGI:3611343

cn4

• Allelic Composition: Prox1^tm2Gco/Prox1⁺; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * NMRI * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:102652 )

• most mutants die within a few days of birth but some survive to adulthood

immune system

abnormal lymph circulation ( J:102652 )

• leakage of chyle from the mesenteric vessels is seen in neonates that die postnatally, but not in surviving adults

abnormal lymphatic vessel morphology ( J:102652 )

• lymph vessels are mispatterned and dilated similar to Prox1^tm1Gco heterozygotes

digestive/alimentary system

abnormal intestine morphology ( J:102652 )

• accumulation of lipid is seen in the intestine walls

growth/size/body

increased susceptibility to age related obesity ( J:102652 )

• some mutants display weight gain similar to Prox1^tm1Gco heterozygotes, but the occurrence is decreased

homeostasis/metabolism

edema ( J:102652 )

• at E14.5 edema is seen identical to that in Prox1^tm1Gco heterozygotes

chylothorax ( J:102652 )

• mutants that die within a few days of birth have milky chylous ascites in the peritoneal cavity and thoracic cavity; however, leakage is not seen in surviving adults

cardiovascular system

abnormal lymph circulation ( J:102652 )

• leakage of chyle from the mesenteric vessels is seen in neonates that die postnatally, but not in surviving adults

respiratory system

chylothorax ( J:102652 )

• mutants that die within a few days of birth have milky chylous ascites in the peritoneal cavity and thoracic cavity; however, leakage is not seen in surviving adults