Phenotypes associated with this allele

• Allele Symbol: Th^tm2Rpa
• Allele Name: targeted mutation 2, Richard D Palmiter
• Allele ID: MGI:2181959
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Th^tm2Rpa/Th^tm2Rpa	involves: 129S7/SvEvBrd * C57BL/6	MGI:3623121

Genotype
MGI:3623121

hm1

• Allelic Composition: Th^tm2Rpa/Th^tm2Rpa
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

mortality/aging

postnatal lethality, complete penetrance ( J:24347 )

• Background Sensitivity: only ~2.6% of homozygotes are born alive on an outbred genetic background; in contrast, no born homozygotes are identified out of 129/Sv inbred offspring

• all naturally born homozygotes (~2.6%) die within 4 weeks, with most deaths occurring by P21

• similarly, all rescued homozygotes die within 5 weeks, with no survivors identified at P35

lethality throughout fetal growth and development, incomplete penetrance ( J:24347 )

• only 5% of homozygotes are recovered at E15.5; only 2.6% of pups born are homozygous

embryonic lethality during organogenesis, incomplete penetrance ( J:24347 )

• ~90% of homozygotes die between E11.5 and E15.5, apparently of cardiovascular failure

• treatment of pregnant females at stage E8.5 of pregnancy with 0.25 mg/ml of L-DOPA rescues ~50% of homozygotes to E17.5 or birth, whereas 1 mg/ml of L-DOPA rescues all homozygotes to birth

• treatment of pregnant females with 1 mg/ml of L-DOPA from E10.5 to E13.5, results in only partial rescue in utero, suggesting a continuous requirement for catecholamines

• treatment of pregnant females with 0.5 mg/ml of DOPS only partially rescues homozygotes to birth, suggesting a requirement for dopamine in addition to noradrenaline

cardiovascular system

blood vessel congestion ( J:24347 )

• at E12.5-E15.5, 6 of 14 homozygotes display congestion of blood in the liver and major blood vessels

liver vascular congestion ( J:24347 )

• at E12.5-E15.5 in 6 of 14 homozygotes

fetal cardiomyocyte disarray ( J:24347 )

• at E12.5, ventricular cardiomyocytes appear less organized

fetal cardiomyocyte vacuoles ( J:24347 )

• at E12.5, ventricular cardiomyocytes appear more vacuolated

abnormal heart atrium morphology ( J:24347 )

• at E12.5, homozygotes with dilated atria exhibit thinning of the atrial wall

dilated heart atrium ( J:24347 )

• at E12.5, 2 of 3 homozygotes display significantly dilated atria

decreased heart rate ( J:24347 )

• at E12.5, homozygotes display slight bradycardia relative to wild-type embryos (37.9 7.5 bpm vs 44.7 9.0 bpm, respectively)

growth/size/body

decreased body size ( J:24347 )

• all homozygotes that survive to term display normal birth weights but become severely runted by P7; similar runting in noted in rescued homozygotes

decreased body weight ( J:24347 )

• by P15, surviving homozygotes weigh ~40% of wild-type littermates

behavior/neurological

abnormal motor coordination/balance ( J:24347 )

• at P15, surviving homozygotes fail to balance on a rotating pencil or walk up an incline

weakness ( J:24347 )

• at P15, both naturally born and rescued homozygotes appear very weak

liver/biliary system

liver vascular congestion ( J:24347 )

• at E12.5-E15.5 in 6 of 14 homozygotes