Phenotypes associated with this allele

• Allele Symbol: Alpk3^{Gt(OST149512)Lex}
• Allele Name: gene trap OST149512, Lexicon Genetics
• Allele ID: MGI:4206048
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Alpk3^Gt(OST149512)Lex/Alpk3^Gt(OST149512)Lex	involves: 129S5/SvEvBrd * C57BL/6J	MGI:5661347

Genotype
MGI:5661347

hm1

• Allelic Composition: Alpk3^{Gt(OST149512)Lex}/Alpk3^{Gt(OST149512)Lex}
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6J

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

cardiovascular system

abnormal heart layer morphology ( J:222361 )

• enlarged hearts exhibit thickened walls of all four chambers and the interventricular septum

abnormal myocardium layer morphology ( J:222361 )

• a mild increase in non-myofibrillar and extracellular space is observed

• however, no increases in interstitial fibrosis or inflammation are observed

abnormal myocardial fiber morphology ( J:222361 )

• mutant cardiomyocytes appear to be slightly thicker in most areas of the heart muscle relative to controls

• rather than being arrayed in tight parallel bundles, mutant myofibrils show a looser arrangement and a mild disarray, with increased waviness, overlapping, and crossing of myofibrils within cardiomyocytes

• cell nuclei are often enlarged, rounded, or lobulated and frequently contain large nucleoli

abnormal intercalated disk morphology ( J:222361 )

• mutant intercalated discs are sparse in number and often appear broad, jagged, and less distinct or fragmented

• where present, mutant intercalated discs are often highly convoluted and less electron-dense than wild-type

thick interventricular septum ( J:222361 )

enlarged heart ( J:222361 )

• both female and male homozygotes display heart enlargement during the first month of life

• however, no spontaneous deaths are observed in either sex up to 12 months of age

increased heart weight ( J:222361 )

• at 24 weeks of age, homozygotes display increased absolute heart weight as well as increased heart weight/body weight and heart weight/tibia length ratios relative to wild-type controls

cardiac hypertrophy ( J:222361 )

• at 24 weeks of age, homozygotes display increased absolute heart weight as well as increased heart weight/body weight and heart weight/tibia length ratios relative to wild-type controls

• primary cardiac hypertrophy is indicated by lack of overt malformations in heart valves or large vessels, including aorta, pulmonary, carotid, and femoral arteries

myocardium hypertrophy ( J:222361 )

• myocardial hypertrophy is indicated by the increased thickness of LV and RV walls and by the markedly increased absolute heart weight and increased heart weight/body weight and heart weight/tibia length ratios

dilated heart left ventricle ( J:222361 )

• at 3 months of age, homozygotes show a marked increase in end-diastolic and end-systolic volumes of left ventricle, suggesting LV chamber dilation

thick ventricular wall ( J:222361 )

• at 3 months of age, homozygotes show increased thickness in both septal and LV free walls at end-diastole; however, no significant change in wall thickness is noted at end-systole

• both LV and RV walls exhibit increased thickness relative to wild-type controls

decreased cardiac output ( J:222361 )

• at 3 months of age, homozygotes display reduced cardiac output

decreased cardiac stroke volume ( J:222361 )

• at 3 months of age, homozygotes display reduced stroke volume

decreased cardiac muscle contractility ( J:222361 )

• at 3 months of age, homozygotes display reduced ejection fractions (EFs), given as stroke volume (SV) divided by LV cavity volume at end-diastole (LVEDV)

• at 3 and 9 months of age, homozygotes show similarly reduced EFs relative to wild-type controls (67% at 3 months and 68% at 9 months of age), indicating that EFs do not deteriorate over time

decreased ventricle muscle contractility ( J:222361 )

• MRI functional analysis revealed that naive male homozygotes show a >50% reduction in LV contractility in both septal and LV free walls, as determined by wall thickness change during contraction

abnormal heart left ventricle pressure ( J:222361 )

• homozygotes display markedly increased baseline LV pressures relative to wild-type controls

• in response to dobutamine challenge, homozygotes fail to exhibit increased LV pressure in conjunction with dobutamine-induced increased heart rates, unlike wild-type controls

decreased systemic arterial systolic blood pressure ( J:222361 )

• although grossly normal appearance and behavior, 12-week-old homozygotes show a significant reduction in systolic blood pressure

• however, no obvious conductance abnormalities or arrhythmia are observed at this age

cardiomyopathy ( J:222361 )

• homozygotes develop a non-progressive cardiomyopathy that presents features of both hypertrophic and dilated forms of cardiomyopathy

muscle

abnormal myocardium layer morphology ( J:222361 )

• a mild increase in non-myofibrillar and extracellular space is observed

• however, no increases in interstitial fibrosis or inflammation are observed

abnormal myocardial fiber morphology ( J:222361 )

• mutant cardiomyocytes appear to be slightly thicker in most areas of the heart muscle relative to controls

• rather than being arrayed in tight parallel bundles, mutant myofibrils show a looser arrangement and a mild disarray, with increased waviness, overlapping, and crossing of myofibrils within cardiomyocytes

• cell nuclei are often enlarged, rounded, or lobulated and frequently contain large nucleoli

abnormal intercalated disk morphology ( J:222361 )

• mutant intercalated discs are sparse in number and often appear broad, jagged, and less distinct or fragmented

• where present, mutant intercalated discs are often highly convoluted and less electron-dense than wild-type

myocardium hypertrophy ( J:222361 )

• myocardial hypertrophy is indicated by the increased thickness of LV and RV walls and by the markedly increased absolute heart weight and increased heart weight/body weight and heart weight/tibia length ratios

decreased cardiac muscle contractility ( J:222361 )

• at 3 months of age, homozygotes display reduced ejection fractions (EFs), given as stroke volume (SV) divided by LV cavity volume at end-diastole (LVEDV)

• at 3 and 9 months of age, homozygotes show similarly reduced EFs relative to wild-type controls (67% at 3 months and 68% at 9 months of age), indicating that EFs do not deteriorate over time

decreased ventricle muscle contractility ( J:222361 )

• MRI functional analysis revealed that naive male homozygotes show a >50% reduction in LV contractility in both septal and LV free walls, as determined by wall thickness change during contraction

cardiomyopathy ( J:222361 )

• homozygotes develop a non-progressive cardiomyopathy that presents features of both hypertrophic and dilated forms of cardiomyopathy

growth/size/body

enlarged heart ( J:222361 )

• both female and male homozygotes display heart enlargement during the first month of life

• however, no spontaneous deaths are observed in either sex up to 12 months of age

increased heart weight ( J:222361 )

• at 24 weeks of age, homozygotes display increased absolute heart weight as well as increased heart weight/body weight and heart weight/tibia length ratios relative to wild-type controls

cardiac hypertrophy ( J:222361 )

• at 24 weeks of age, homozygotes display increased absolute heart weight as well as increased heart weight/body weight and heart weight/tibia length ratios relative to wild-type controls

• primary cardiac hypertrophy is indicated by lack of overt malformations in heart valves or large vessels, including aorta, pulmonary, carotid, and femoral arteries

myocardium hypertrophy ( J:222361 )

• myocardial hypertrophy is indicated by the increased thickness of LV and RV walls and by the markedly increased absolute heart weight and increased heart weight/body weight and heart weight/tibia length ratios