Pln<tm1Egk> Targeted Allele Detail MGI Mouse (MGI:2158357)

Pln^tm1Egk
Targeted Allele Detail

Nomenclature

Symbol:	Pln^tm1Egk
Name:	phospholamban; targeted mutation 1, Evangelia G Kranias
MGI ID:	MGI:2158357
Synonyms:	PLB-KO, PLB^-, PLN^-
Gene:	Pln Location: Chr10:53057513-53065787 bp, + strand Genetic Position: Chr10, cytoband B3

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:39745
Parent Cell Line:	D3 (ES Cell)
Strain of Origin:	129S2/SvPas

Mutation
description

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	A 1.8 kb genomic fragment containing the coding sequences of the gene was replaced with a neomycin selection gene lacking a polyadenylation signal. The authors state that no detectable cardiac muscle transcript or protein was produced from this allele (data not shown). (J:39745)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 7 strains available Cell Lines: 0 lines available
Carrying any Pln Mutation:	9 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	hm3	cx4	cx5	cx6	cx7	tg8
behavior/neurological					√
abnormal locomotor activation					√
		hm1	hm2	hm3	cx4	cx5	cx6	cx7	tg8
cardiovascular system		√	√	√	√	√	√	√	√
increased cardiac muscle contractility		√		√		√	√	√
abnormal cardiac muscle relaxation		√			√	√	√
abnormal myocardial fiber physiology		√				√	√
increased heart weight			√		√				√
abnormal blood pressure				√
decreased blood pressure				√
increased blood pressure				√
enlarged myocardial fiber					√
abnormal heart shape					√
cardiac hypertrophy					√			√
thick ventricular wall					√
abnormal cardiac output					√
abnormal cardiac stroke volume					√
decreased heart rate					√			√
congestive heart failure					√
		hm1	hm2	hm3	cx4	cx5	cx6	cx7	tg8
homeostasis/metabolism					√
abnormal calcium ion homeostasis					√
		hm1	hm2	hm3	cx4	cx5	cx6	cx7	tg8
life span/aging					√
premature death					√
		hm1	hm2	hm3	cx4	cx5	cx6	cx7	tg8
muscle		√		√	√	√	√	√
increased cardiac muscle contractility		√		√		√	√	√
abnormal cardiac muscle relaxation		√			√	√	√
enlarged myocardial fiber					√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Pln^tm1Egk/Pln^tm1Egk	involves: 129S2/SvPas
cardiovascular system increased cardiac muscle contractility (J:106044) isolated cardiac myocytes exhibit a significant increase in fractional cell shortening and higher dL/dT values abnormal cardiac muscle relaxation (J:106044) isolated cardiac myocytes exhibit higher relaxation rates (-dL/dt) than wild-type abnormal myocardial fiber physiology (J:106044) under baseline conditions, left ventricular myocytes exhibit an enhanced calcium transient amplitude and faster calcium transient decays left ventricular myocytes do not show an increase in the intracellular calcium transient amplitudes or accelerated calcium transient decays when treated with isoproterenol as is seen in wild-type muscle increased cardiac muscle contractility (J:106044) isolated cardiac myocytes exhibit a significant increase in fractional cell shortening and higher dL/dT values abnormal cardiac muscle relaxation (J:106044) isolated cardiac myocytes exhibit higher relaxation rates (-dL/dt) than wild-type
Genotype	Allelic Composition	Genetic Background
hm2	Pln^tm1Egk/Pln^tm1Egk	involves: 129S2/SvPas * CF-1 * FVB/N
cardiovascular system increased heart weight (J:134706) the heart weight to body weight ratio is 10% greater compared to controls
Genotype	Allelic Composition	Genetic Background
hm3	Pln^tm1Egk/Pln^tm1Egk	involves: 129S2/SvPas * CF1
cardiovascular system abnormal blood pressure (J:39745) decreased blood pressure (J:39745) diastolic and end diastolic pressures were decreased rates of pressure development were increased increased blood pressure (J:39745) systolic intraventricular pressure increased rates of pressure development were increased increased cardiac muscle contractility (J:39745, J:59967) no increased contractility in response to beta-adrenergic agonists (J:39745) large force developed at low frequencies of stimulation but more like controls at higher frequencies (J:59967) no acceleration of time to peak tension with increasing frequency of stimulation, similar observation for relaxation time (J:59967) declining rate of force development with increased frequency of stimulation (J:59967) muscle increased cardiac muscle contractility (J:39745, J:59967) no increased contractility in response to beta-adrenergic agonists (J:39745) large force developed at low frequencies of stimulation but more like controls at higher frequencies (J:59967) no acceleration of time to peak tension with increasing frequency of stimulation, similar observation for relaxation time (J:59967) declining rate of force development with increased frequency of stimulation (J:59967)
Genotype	Allelic Composition	Genetic Background
cx4	Atp2a2^tm1Fwuy/Atp2a2^tm1Fwuy Pln^tm1Egk/Pln^tm1Egk	involves: 129 * FVB/N * Swiss
cardiovascular system enlarged myocardial fiber (J:110974) the cardiomyocyte dimensions in double homozygous mice were increased to a much larger extent than in single Atp2a2^tm1Fwuy homozygous mice abnormal heart shape (J:110974) the hearts from double homozygous mice were more hypertrophic and balloon-shaped than the heart from single Atp2a2^tm1Fwuy homozygous mice increased heart weight (J:110974) in double homozygous mice, heart weight/body weight ratios and heart weight/tibial length ratios are increased compared to wild-type cardiac hypertrophy (J:110974) in double homozygous mice at 12-16 weeks, concentric hypertrophy was aggravated compared to single Atp2a2^tm1Fwuy homozygous mice thick ventricular wall (J:110974) in double homozygous mice at 12-16 weeks, echocardiographic measurements showed thicker posterior wall than single Atp2a2^tm1Fwuy homozygous mice showed a larger LV mass-measured as cross-sectional area LV wall thickening was not the result of increased interstitial fibrosis abnormal cardiac output (J:110974) beta-adrenergic stimulation in double homozygous mice failed to increase the cardiac output abnormal cardiac stroke volume (J:110974) maximal and minimal LV volume and stroke volume appeared lower in double homozygous mice at 12-16 weeks abnormal cardiac muscle relaxation (J:110974) impaired LV relaxation assessed by dP/dt min in double homozygous mice at 12-16 weeks compared to wild-type mice contractility assessed by dP/dt max were normal decreased heart rate (J:110974) in double homozygous mice at 12-16 weeks compared to wild-type congestive heart failure (J:110974) two out of 16 double homozygous mice died after completing running performance test on a rodent treadmill displaying clinical signs of congestive heart failure beta-adrenergic stimulation impaired LV contractility and relaxation and caused acute heart failure during the procedure life span/aging premature death (J:110974) the life span of mutant mice was severely shortened at 496 average age in days behavior/neurological abnormal locomotor activation (J:110974) the spontaneous activity was severely reduced in double homozygous mice at 12-16 weeks of age compared to wild-type and single Atp2a2^tm1Fwuy homozygous mice homeostasis/metabolism abnormal calcium ion homeostasis (J:110974) the maximal pumping capacity of sarcoplasmic reticulum calcium ion uptake was reduced by 50% in cardiac homogenate of homozygous mutant mice muscle enlarged myocardial fiber (J:110974) the cardiomyocyte dimensions in double homozygous mice were increased to a much larger extent than in single Atp2a2^tm1Fwuy homozygous mice abnormal cardiac muscle relaxation (J:110974) impaired LV relaxation assessed by dP/dt min in double homozygous mice at 12-16 weeks compared to wild-type mice contractility assessed by dP/dt max were normal
Genotype	Allelic Composition	Genetic Background
cx5	Hprt^tm1Dhm/Hprt^tm1Dhm Pln^tm1Egk/Pln^tm1Egk	involves: 129P2/OlaHsd * 129S2/SvPas
cardiovascular system increased cardiac muscle contractility (J:106044) isolated cardiac myocytes exhibit enhanced fractional cell shortening and higher dL/dT values compared to wild-type, however this shortening and dL/dT values are less than that seen in the single homozygous Pln mutant mouse abnormal cardiac muscle relaxation (J:106044) isolated cardiac myocytes exhibit higher relaxation rates (-dL/dt) than wild-type but lower than that seen in single homozygous Pln mutant mice abnormal myocardial fiber physiology (J:106044) under baseline conditions, left ventricular myocytes exhibit faster calcium transient decays than wild-type, however they are slower than in single homozygous Pln mutant mice muscle increased cardiac muscle contractility (J:106044) isolated cardiac myocytes exhibit enhanced fractional cell shortening and higher dL/dT values compared to wild-type, however this shortening and dL/dT values are less than that seen in the single homozygous Pln mutant mouse abnormal cardiac muscle relaxation (J:106044) isolated cardiac myocytes exhibit higher relaxation rates (-dL/dt) than wild-type but lower than that seen in single homozygous Pln mutant mice
Genotype	Allelic Composition	Genetic Background
cx6	Hprt^tm1Dhm/Y Pln^tm1Egk/Pln^tm1Egk	involves: 129P2/OlaHsd * 129S2/SvPas
cardiovascular system increased cardiac muscle contractility (J:106044) isolated cardiac myocytes exhibit enhanced fractional cell shortening and higher dL/dT values compared to wild-type, however this shortening and dL/dT values are less than that seen in the single homozygous Pln mutant mouse abnormal cardiac muscle relaxation (J:106044) isolated cardiac myocytes exhibit higher relaxation rates (-dL/dt) than wild-type but lower than that seen in single homozygous Pln mutant mice abnormal myocardial fiber physiology (J:106044) under baseline conditions, left ventricular myocytes exhibit faster calcium transient decays than wild-type, however they are slower than in single homozygous Pln mutant mice muscle increased cardiac muscle contractility (J:106044) isolated cardiac myocytes exhibit enhanced fractional cell shortening and higher dL/dT values compared to wild-type, however this shortening and dL/dT values are less than that seen in the single homozygous Pln mutant mouse abnormal cardiac muscle relaxation (J:106044) isolated cardiac myocytes exhibit higher relaxation rates (-dL/dt) than wild-type but lower than that seen in single homozygous Pln mutant mice
Genotype	Allelic Composition	Genetic Background
cx7	Csrp3^tm1Crni/Csrp3^tm1Crni Pln^tm1Egk/Pln^tm1Egk	involves: 129S2/SvPas * CF1
cardiovascular system cardiac hypertrophy (J:58299) indicated by a slight increase in the heart weight/body weight ratio heart structure is otherwise normalized compared to conditions in mice homozygous for with Csrp3^Tm1Crni only more normal heart size normalized myofibrillar organization no fibrosis normal cardiac chamber dimensions as indicated by echocardiography increased cardiac muscle contractility (J:58299) increased contractile properties similar to those of mice homozygous for Pln^tm1Egk only normalized left ventricular relaxation and diastolic function decreased heart rate (J:58299) slightly decreased relative to wild-type muscle increased cardiac muscle contractility (J:58299) increased contractile properties similar to those of mice homozygous for Pln^tm1Egk only normalized left ventricular relaxation and diastolic function
Genotype	Allelic Composition	Genetic Background
tg8	Pln^tm1Egk/Pln^tm1Egk Tg(Myh6*)140Lnwd/0	involves: 129S2/SvPas * CBA * CF-1 * FVB/N
cardiovascular system increased heart weight (J:134706) the heart weight to body weight ratio is 30% greater compared to controls

References

Original:	J:39745 Luo W et al., "Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation." Circ Res 1994 Sep;75(3):401-9
All:	45 reference(s)

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