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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Alpk3Gt(OST149512)Lex
gene trap OST149512, Lexicon Genetics
MGI:4206048
Summary 1 genotype
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Alpk3Gt(OST149512)Lex/Alpk3Gt(OST149512)Lex involves: 129S5/SvEvBrd * C57BL/6J MGI:5661347


Genotype
MGI:5661347
hm1
Allelic
Composition
Alpk3Gt(OST149512)Lex/Alpk3Gt(OST149512)Lex
Genetic
Background
involves: 129S5/SvEvBrd * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alpk3Gt(OST149512)Lex mutation (1 available); any Alpk3 mutation (66 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• enlarged hearts exhibit thickened walls of all four chambers and the interventricular septum
• a mild increase in non-myofibrillar and extracellular space is observed
• however, no increases in interstitial fibrosis or inflammation are observed
• 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
• 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
• 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
• 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
• 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
• 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
• at 3 months of age, homozygotes show a marked increase in end-diastolic and end-systolic volumes of left ventricle, suggesting LV chamber dilation
• 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
• at 3 months of age, homozygotes display reduced cardiac output
• at 3 months of age, homozygotes display reduced stroke volume
• 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
• 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
• 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
• 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
• homozygotes develop a non-progressive cardiomyopathy that presents features of both hypertrophic and dilated forms of cardiomyopathy

muscle
• a mild increase in non-myofibrillar and extracellular space is observed
• however, no increases in interstitial fibrosis or inflammation are observed
• 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
• 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
• 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
• 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
• 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
• homozygotes develop a non-progressive cardiomyopathy that presents features of both hypertrophic and dilated forms of cardiomyopathy

growth/size/body
• 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
• 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
• 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
• 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





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last database update
11/19/2024
MGI 6.24
The Jackson Laboratory