Phenotypes associated with this allele

• Allele Symbol: Hnrnpu^tm1.1Tman
• Allele Name: targeted mutation 1.1, Tom Maniatis
• Allele ID: MGI:5648110
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman	involves: 129S4/SvJaeSor	MGI:5829558
cn2	Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJaeSor * FVB	MGI:5829560
cn3	Gt(ROSA)26Sor^tm1(CAG-GCaMP5)Ryba/Gt(ROSA)26Sor^+ Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJaeSor * FVB	MGI:5829563
cn4	Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * FVB/N	MGI:5829559

Genotype
MGI:5829558

hm1

• Allelic Composition: Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman
• Genetic Background: involves: 129S4/SvJaeSor

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

normal phenotype

no abnormal phenotype detected ( J:223139 )

• mice are phenotypically indistinguishable from wild-type controls

Genotype
MGI:5829560

cn2

• Allelic Composition: Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJaeSor * FVB

Aberrant cardiomyocyte oranization and contractility in Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman Tg(Ckmm-cre)5Khn/0 hearts

mortality/aging

postnatal lethality, complete penetrance ( J:223139 )

• although born at normal Mendelian ratios, all mice die abruptly from heart failure around 14 days after birth

cardiovascular system

abnormal myocardial fiber morphology ( J:223139 )

• cardiomyocytes appear disorganized, slightly hypertrophic, and are surrounded by more white space upon H&E staining

• trichrome staining revealed an increased blue signal between cardiomyocytes, suggesting increased expression of the extracellular matrix

• cardiomyocytes show abnormal actin dynamics and shortened sarcomeres

decreased myocardial fiber number ( J:223139 )

• overall density of cardiomyocytes is reduced, likely due to heart remodeling

increased myocardial fiber size ( J:223139 )

• cardiomyocytes appear slightly hypertrophic

• however, no major cardiac hypertrophy is observed at P12

thin interventricular septum ( J:223139 )

• thinning of the ventricle septum is noted at P14

thin ventricular wall ( J:223139 )

• thinning of the ventricle wall is noted at P14

dilated heart ventricle ( J:223139 )

• mice show progressive dilation of the heart ventricle chambers

dilated heart left ventricle ( J:223139 )

• dilation of the left ventricle chamber is observed as early as P7

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

decreased heart ventricle muscle contractility ( J:223139 )

• fractional shortening (FS) is significantly reduced (below 20%) relative to controls (above 60%)

• reduced FS is detected as early as P6, and this decrease progresses rapidly to the time of death

decreased cardiac muscle relaxation ( J:223139 )

• ability of sarcomeres to fully relax is impaired in cardiomyocytes

abnormal heart echocardiography feature ( J:223139 )

• at P11, B- and M-mode images of echocardiography show a dramatic increase of left ventricular anterior-to-posterior wall diameter during systole and diastole

abnormal myocardial fiber physiology ( J:223139 )

• cardiomyocytes show abnormal actin dynamics and contractility defects

congestive heart failure ( J:223139 )

• cardiac malfunction starts early after birth and progresses rapidly to cardiac failure

• however, no differences in heart rate are observed from P3 to P11

muscle

abnormal myocardial fiber morphology ( J:223139 )

• cardiomyocytes appear disorganized, slightly hypertrophic, and are surrounded by more white space upon H&E staining

• trichrome staining revealed an increased blue signal between cardiomyocytes, suggesting increased expression of the extracellular matrix

• cardiomyocytes show abnormal actin dynamics and shortened sarcomeres

decreased myocardial fiber number ( J:223139 )

• overall density of cardiomyocytes is reduced, likely due to heart remodeling

increased myocardial fiber size ( J:223139 )

• cardiomyocytes appear slightly hypertrophic

• however, no major cardiac hypertrophy is observed at P12

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

decreased heart ventricle muscle contractility ( J:223139 )

• fractional shortening (FS) is significantly reduced (below 20%) relative to controls (above 60%)

• reduced FS is detected as early as P6, and this decrease progresses rapidly to the time of death

decreased cardiac muscle relaxation ( J:223139 )

• ability of sarcomeres to fully relax is impaired in cardiomyocytes

increased cardiomyocyte apoptosis ( J:223139 )

• at P13, hearts exhibit a slightly higher level of apoptosis than control hearts, as determined by cleaved caspase 3 staining

abnormal sarcomere morphology ( J:223139 )

• under conditions of muscle relaxation, the lengths of sarcomeres and I bands are markedly reduced in cardiomyocytes

• at P11, the average length of sarcomeres (Z line to Z line) is only 1.68 um versus ~2.24 um in controls

• some regions of sarcomeres lack mitochondria coverage

abnormal I band morphology ( J:223139 )

• the lengths of I bands are markedly reduced in cardiomyocytes

cellular

decreased mitochondrial number ( J:223139 )

• some regions of sarcomeres lack mitochondria coverage

increased cardiomyocyte apoptosis ( J:223139 )

• at P13, hearts exhibit a slightly higher level of apoptosis than control hearts, as determined by cleaved caspase 3 staining

Genotype
MGI:5829563

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-GCaMP5)Ryba}/Gt(ROSA)26Sor⁺; Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S4/SvJaeSor * FVB

cardiovascular system

decreased cardiac muscle contractility ( J:223139 )

• amplitude of heart contraction is significantly reduced relative to that in control hearts

• analysis of calcium cycling and heart contraction revealed impaired calcium handling

• hearts reach the maximal calcium level slightly slower than control hearts

• rate of post-contraction calcium decrease is significantly slower than that in controls hearts

• calcium decays almost linearly from the peak signal, in contrast to a two-phase (a rapid drop within the first 20 ms followed by a slower decrease for about 200 ms) reduction in control hearts

muscle

decreased cardiac muscle contractility ( J:223139 )

• amplitude of heart contraction is significantly reduced relative to that in control hearts

• analysis of calcium cycling and heart contraction revealed impaired calcium handling

• hearts reach the maximal calcium level slightly slower than control hearts

• rate of post-contraction calcium decrease is significantly slower than that in controls hearts

• calcium decays almost linearly from the peak signal, in contrast to a two-phase (a rapid drop within the first 20 ms followed by a slower decrease for about 200 ms) reduction in control hearts

Genotype
MGI:5829559

cn4

• Allelic Composition: Hnrnpu^tm1.1Tman/Hnrnpu^tm1.1Tman; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:223139 )

• although born at normal Mendelian ratios, all mice die abruptly from heart failure at exactly 10 days after birth

cardiovascular system

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy

congestive heart failure ( J:223139 )

muscle

dilated cardiomyopathy ( J:223139 )

• mice develop severe, lethal dilated cardiomyopathy