Mouse Genome Informatics
cn1
    Adipor1tm2Tka/Adipor1tm2Tka
Tg(Ckmm-cre)5Khn/0

B6.Cg-Adipor1tm2Tka Tg(Ckmm-cre)5Khn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• mice exhibit lower muscle endurance in an involuntary physical exercise test compared with wild-type mice
• in skeletal muscle
• following glucose administration
• following glucose administration
• muscles exhibit decreased insulin sensitivity compared with wild-type mice with decreased glucose disposal and glucose infusion rate
• however, treatment with resveratrol or two weeks of exercise ameliorates insulin resistance while treatment with MnTBAP produces a trend towards amelioration of insulin resistance
• in skeletal muscle

cellular
• skeletal muscle exhibits a decrease in mitochondrial DNA content compared with wild-type muscle
• however, treatment with resveratrol, Bay-K 8644 (a calcium-channel opener), or two weeks of exercise increased mitochondrial content
• skeletal muscle cells exhibit a decrease in beta oxidation and an increased in hydrogen peroxide level compared with wild-type cells
• however, treatment with MnTBAP reduces hydrogen peroxide levels

muscle
• soleus muscle exhibit a decrease in type I fibers compared with wild-type muscles

behavior/neurological
• mice exhibit lower muscle endurance in an involuntary physical exercise test compared with wild-type mice


Mouse Genome Informatics
cn2
    Nuak1tm1Esu/Nuak1tm1Esu
Tg(Ckmm-cre)5Khn/0

B6.Cg-Nuak1tm1Esu Tg(Ckmm-cre)5Khn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• no differences are detected in heart or soleus muscle weights and soleus myocyte cross sections are similar to controls on both normal chow and high fat diets (J:185463)
• in mice fed a normal chow or high fat diet compared to diet matched controls
• in soleus muscle cells from mice on a high fat diet glucose uptake is similar to mice on a normal chow diet unlike in wild-type mice where the high fat diet impairs glucose uptake

homeostasis/metabolism
• in mice on a high fat diet, fasting glucose levels are reduced at 13 - 15 and 18-19 weeks of age compared to diet matched controls
• no difference in glucose levels compared to controls is detected in mice on a normal chow diet
• in mice on a high fat diet compared to diet matched controls
• in mice fed a normal chow or high fat diet compared to diet matched controls
• in mice on a high fat diet compared to diet matched controls


Mouse Genome Informatics
cn3
    Sgcatm2Kcam/Sgcatm2Kcam
Tg(Ckmm-cre)5Khn/0

either: (involves: 129S4/SvJae * 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6J * FVB)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• conditional mutants fail to develop muscular dystrophy pathology; striated and cardiac muscle show expression of mutant alpha-sarcoglycan, as well as sarcospan (J:130252)
• percentage of fibers with centrally located nuclei are normalized to levels of heterozygous non-transgenic controls (J:130252)

homeostasis/metabolism
N
• serum creatine kinase levels are normalized (J:130252)


Mouse Genome Informatics
cn4
    Igf1rtm1.1Mhz/Igf1r+
Insrtm1Khn/Insrtm1Khn
Tg(Ckmm-cre)5Khn/0

involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 3 of 13 mice die by 6 months of age

cardiovascular system
• at P17, left ventricular fractional shortening is reduced 23% compared to Igf1rtm1.1Mhz Insrtm1Khn homozygote controls

respiratory system
• beginning at 3 months of age, 1 of 13 mice appear to gasp for air

behavior/neurological
• beginning at 3 months of age, 1 of 13 mice exhibit less activity than wild-type mice

muscle
• at P17, left ventricular fractional shortening is reduced 23% compared to Igf1rtm1.1Mhz Insrtm1Khn homozygote controls

homeostasis/metabolism
N
• mice exhibit normal glucose homeostasis (J:118987)


Mouse Genome Informatics
cn5
    Igf1rtm1.1Mhz/Igf1rtm1.1Mhz
Insrtm1Khn/Insrtm1Khn
Tg(Ckmm-cre)5Khn/0

involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within the first month usually after birth 2 days after beginning to gasp for air at P16
• death is either spontaneous or precipitated by the stress of routine handling

cardiovascular system
• mice exhibit irregular and disrupted sarcomeric Z and M lines and increased mitochondria with central crowding compared to wild-type hearts
• at P8 and P20, heart weights reduced 15% and 25%, respectively, compared to in wild-type mice
• mice exhibit decreased heart weight to body weight
• at P17, mice exhibit an increase in left ventricle diameter of 6.7% in diastolic and 57.1% in systolic states
• at P17, left ventricular fractional shortening is reduced 33% compared to Igf1rtm1.1Mhz Insrtm1Khn homozygote controls

behavior/neurological
• at P16, mice become less active than wild-type mice

respiratory system
• at P16, mice gasp for air

growth/size
• at P20, mice weigh 15% to 20% less than wild-type mice
• despite normal growth rates during the first two weeks after birth, mice exhibit reduced growth rates during week 3

muscle
• mice exhibit irregular and disrupted sarcomeric Z and M lines and increased mitochondria with central crowding compared to wild-type hearts
• at P17, left ventricular fractional shortening is reduced 33% compared to Igf1rtm1.1Mhz Insrtm1Khn homozygote controls

homeostasis/metabolism
N
• mice exhibit normal glucose homeostasis (J:118987)


Mouse Genome Informatics
cn6
    Igf1rtm1.1Mhz/Igf1rtm1.1Mhz
Insrtm1Khn/Insr+
Tg(Ckmm-cre)5Khn/0

involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• heart function and morphology is normal (J:118987)

growth/size
N
• mice exhibit normal growth rates (J:118987)

homeostasis/metabolism
N
• mice exhibit normal glucose homeostasis (J:118987)


Mouse Genome Informatics
cn7
    Slc2a4tm1Abel/Slc2a4tm1Abel
Tg(Ckmm-cre)5Khn/?

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• growth was normal up to about 6 months
• weight gain became slower in older animals
• heart weight to body weight ratio increased 55% by 10 weeks of age

homeostasis/metabolism
• fasting and fed blood glucose levels increased from 2 to 4 months and then plateaued
• at 4 months both fed and fasted mice were hyperglycemic
• impaired glucose tolerance by 2 months and progressed until 4 months
• liver glycogen levels up 450%, comparable to increase in glucose uptake by liver
• as early as 8 weeks in muscle
• glucose levels did not decrease in males in response to insulin injection and decreased by 34% in females
• cholesterol and free faty acid levels normal to 6 months of age
• fasting beta-hydroxybuterate levels lowered

muscle
N
• muscle mass was normal (J:75418)
• lactate levels in muscles of male mice were reduced
• basal glucose uptake reduced 73-88% in skeletal muscle
• insulin and contraction both fail to stimulate glucose transport

liver/biliary system
• liver glycogen levels up 450%, comparable to increase in glucose uptake by liver


Mouse Genome Informatics
cn8
    Ptpn11tm1Ambt/Ptpn11tm1Ambt
Tg(Ckmm-cre)5Khn/0

involves: 129/Sv * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• exhibit a decrease in skeletal myofiber size concomitant with a reduction in larger myofibers as well as a decrease in myonuclear number
• exhibit a decrease in the number of skeletal muscle fibers, more specifically a reduction in type I slow muscle fibers


Mouse Genome Informatics
cn9
    Igf1rtm1.1Mhz/Igf1rtm1.1Mhz
Tg(Ckmm-cre)5Khn/0

involves: 129/Sv * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• mice exhibit increased heart weight
• however, heart function is normal

growth/size
N
• mice exhibit normal growth rates (J:118987)

homeostasis/metabolism
N
• mice exhibit normal glucose homeostasis (J:118987)


Mouse Genome Informatics
cn10
    Plectm1Gwi/Plectm4Gwi
Tg(Ckmm-cre)5Khn/?

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased survival rates starting at 6 months of age

muscle
N
• no abnormal muscle phenotype in early months of life (J:137067)
• extensor digitorum longus is normal at 16 months of age (J:137067)
• focal disorganization of contractile apparatus
• detached from the contractile apparatus in the soleus and the diaphragm
• 61% of fibers with focal detachments at 8 weeks
• inner structure of fibers is disorganized
• eosinophylic inclusions are present under the sarcolemma
• hypertrophic and split fibers in both the soleus and diaphragm in older mice
• centrally nucleated fibers are present in the soleus at 8 weeks
• at 3 months, 35% of fibers in exercised mice are centrally nucleated (45% at 12 months)
• slight reduction in total number of fibers
• numerous necrotic fibers are found in the soleus at 8 weeks
• soleus muscle appears pale at 8 weeks of age and pathological changes are seen at 6 months
• loss of muscle mass observed in some mice at 16 months of age
• atrophic fibers found in then soleus at 1 year

cardiovascular system
N
• no heart pathologies at 12 months (J:137067)
• no dilated or hypertrophic cardiomyopathies at 16 months of age (J:137067)
• increased connective tissue at 16 months of age
• focal disorganization of contractile apparatus

homeostasis/metabolism
• decreased endurance during voluntary wheel running

cellular
• mitochondria lose association with Z-discs of muscle fibers
• mitochondria found in focal aggregates in sarcoplasm and subsarcolemmal regions
• numbers of mitochondria in muscle fibers is reduced

behavior/neurological
• decreased endurance during voluntary wheel running


Mouse Genome Informatics
cn11
    Bcar1tm2.1Homy/Bcar1tm2.1Homy
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• mice exhibit normal basic skeletal muscle properties and exercise-induced fiber-type transformation (J:195063)


Mouse Genome Informatics
cn12
    Prkcitm1Rfar/Prkci+
Tg(Ckmm-cre)5Khn/?

involves: 129P2/OlaHsd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• males and females have more serum lipid than wild-type mice
• serum free fatty acid levels are increased by 90% relative to wild-type mice
• fasting triglyceride levels are increased relative to in wild-type mice
• in a euglycemic clamp assay, mice require a reduced rate of glucose infusion compared to wild-type mice to maintain euglycemia
• in mice fed ad libitum, serum glucose levels are increased
• fasting glucose levels during insulin and glucose tolerance tests is increased by 20% to 25%
• when dietary fat content is increased from 5% to 10% for 2 months, mice exhibit higher glucose levels than in wild-type mice at all time points and during fasting glucose tolerance testing
• in mice fed ad libitum, serum insulin levels are increased
• in mice fed ad libitum, glucose tolerance impairment is comparable to or more severe than in homozygotes
• in mice fed ad libitum, insulin tolerance is impairment is comparable to or more severe than in homozygotes
• in a euglycemic clamp assay, whole-body insulin resistance is accounted for by decreases in insulin-stimulated whole-body glucose uptake and muscle glucose uptake of 25% and 30%, respectively

muscle
• insulin-stimulated uptake of glucose and [3H]2-deoxyglucose in vastus laterallis, soleus and extensor digitorum longus, and heart muscles is reduced by 50% to 60% compared to in wild-type mice

liver/biliary system
• even on a low-fat diet, hepatostetosis occurs and is more pronounced in heterogyzotes than in homozygotes

adipose tissue
• insulin-stimulated glucose transport is impaired

growth/size
• body weight is increased relative to wild-type mice and homozygous mice
• mice develop an obesity/diabetes syndrome associated with increased food intake

behavior/neurological
• mice consume 20% more regular chow than wild-type mice

immune system
• mice develop an obesity/diabetes syndrome associated with increased food intake

endocrine/exocrine glands


Mouse Genome Informatics
cn13
    Cebpbtm1Nerl/Cebpbtm1Nerl
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mice exhibit normal muscle regeneration in response to treatment with cardiotoxin (J:153686)

muscle
N
• mice exhibit normal muscle regeneration in response to treatment with cardiotoxin (J:153686)


Mouse Genome Informatics
cn14
    Abhd5tm1Rze/Abhd5tm1Rze
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

homeostasis/metabolism
N
• mitochondrial fatty acid oxidation and triglyceride hydrolutic activities in skeletal muscle are normal (J:197835)
• mice exhibit normal insulin sensitivity (J:197835)
• in cardiac muscle
• during the light and dark phase
• glucose clearance is enhanced
• in fasted mice
• in re-fed mice
• exercised mice fail to exhibit a decrease in the skeletal muscle indicating a defect in skeletal muscle triglyceride catabolism compared with control mice
• in non-exercised and exercised mice
• exercised mice fail to exhibit a decrease in the skeletal muscle compared with control mice
• moderate in fasted mice
• 43-fold in the cardiac muscle of non-fasted mice
• 15-fold in the cardiac muscle of fasted mice
• in skeletal muscle
• in cardiac muscle
• however, in vitro triglyceride hydrolytic activity in skeletal muscle is normal
• mild increase in LPA acyltransferase activity

cardiovascular system
• septal and posterial wall thickening
• increased 6.7-fold
• however, glucose uptake in skeletal muscle, liver and adipose tissue is normal

muscle
• increased 6.7-fold
• however, glucose uptake in skeletal muscle, liver and adipose tissue is normal

liver/biliary system
• moderate in fasted mice


Mouse Genome Informatics
cn15
    Plectm4Gwi/Plectm4Gwi
Tg(Ckmm-cre)5Khn/?

involves: 129P2/OlaHsd * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased survival rates starting at 6 months of age

muscle
N
• no abnormal muscle phenotype in early months of life (J:137067)
• extensor digitorum longus is normal at 16 months of age (J:137067)
• focal disorganization of contractile apparatus
• detached from the contractile apparatus in the soleus and the diaphragm
• 61% of fibers with focal detachments at 8 weeks
• inner structure of fibers disorganized
• eosinophylic inclusions under the sarcolemma
• hypertrophic and split fibers in both the soleus and diaphragm in older mice
• numerous centrally nucleated fibers in the soleus at 8 weeks
• at 3 months, 35% of fibers in exercised mice are centrally nucleated (45% at 12 months)
• slight reduction in total number of fibers
• numerous necrotic fibers in the soleus at 8 weeks
• soleus muscle appears pale at 8 weeks of age and pathological changes are seen at 6 months
• loss of muscle mass observed in some mice at 16 months of age
• atrophic fibers in soleus at 1 year

cardiovascular system
N
• no heart pathologies at 12 months (J:137067)
• no dilated or hypertrophic cardiomyopathies at 16 months of age (J:137067)
• increased connective tissue at 16 months of age
• focal disorganization of contractile apparatus

cellular
• mitochondria lose association with Z-discs of muscle fibers
• mitochondria found in focal aggregates in sarcoplasm and subsarcolemmal regions
• numbers of mitochondria in muscle fibers is reduced

homeostasis/metabolism
• decreased endurance during voluntary wheel running

behavior/neurological
• decreased endurance during voluntary wheel running


Mouse Genome Informatics
cn16
    Ptentm2Mak/Ptentm2Mak
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• exhibit an increase in the anterior wall thickness, however see no evidence of wall thinning or tissue fibrosis and heart rate is normal
• increase in both the length and width of cardiomyocytes
• increased in heart size is detectable in newborns
• seen at 10 weeks and 12 months of age, however do not observe cardiac decompensation or dilated cardiomyopathy
• exhibit an increase in the left ventricle mass
• decrease in fractional shortening, velocity of circumferential fiber shortening, peak aortic outflow velocity, dP/dT-max and dP/dT-min, indicating impaired contractile heart function
• individual cardiomyocytes display a reduction in contractility as shown by a reduction in percent cell shortening and positive and negative dL/dTs

muscle
• increase in both the length and width of cardiomyocytes
• decrease in fractional shortening, velocity of circumferential fiber shortening, peak aortic outflow velocity, dP/dT-max and dP/dT-min, indicating impaired contractile heart function
• individual cardiomyocytes display a reduction in contractility as shown by a reduction in percent cell shortening and positive and negative dL/dTs


Mouse Genome Informatics
cn17
    Pik3cgtm1Pngr/Pik3cgtm1Pngr
Ptentm2Mak/Ptentm2Mak
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• significantly enlarged compared to wild-type and single homozygous Pik3cgtm1Pngr mice
• extent of cardiac hypertrophy is similar to that seen in mice with cardiomyocyte-specific inactivation of Pten
• hearts are hypercontractile as assessed by increased fractional shortening, velocity or circumferential fiber shortening, and peak aortic outflow velocity
• individual cardiomyocytes display increased contractility despite the hypertrophy

muscle
• hearts are hypercontractile as assessed by increased fractional shortening, velocity or circumferential fiber shortening, and peak aortic outflow velocity
• individual cardiomyocytes display increased contractility despite the hypertrophy


Mouse Genome Informatics
cn18
    Ptentm2Mak/Ptentm2Mak
Tg(Ckmm-cre)5Khn/0
Tg(Myh6-Pik3ca)1Siz/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• display a reduction in heart size similar to that seen in single Tg(Myh6-Pik3ca)1Siz mice

muscle


Mouse Genome Informatics
cn19
    Aifm1tm2Pngr/Y
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• male mutants appear normal at 2 months; at 3 months, they display significant weight loss (J:113016)

cellular
• mitochondria display abnormal morphology at 9 weeks but not at 4 weeks of age (J:113016)
• mitochondria display marked cristolysis at 9 weeks but not at 4 weeks of age
• heart muscle has increased number of mitochondria (J:113016)
• lipid peroxidation markers are increased >2.5 fold in 9-week old mutants indicating impaired mitochondrial respiration (J:113016)
• a significant increase in lactate/pyruvate ratio is observed (J:113016)
• complex I respiratory chain complex is reduced to ~50% of control levels in heart and gastrocnemius at 5 weeks of age, while complex III level is ~90% of control in heart and gastrocnemius (J:113016)
• respiratory chain enzyme activities in soleus, gastrocnemium and heart muscle is severely reduced; complex I activity in skeletal muscle and heart is reduced (up to 80%) while complex IV activity in the heart is more mildly reduced at 18 weeks of age (J:113016)
• lipid peroxidation markers (indicators or oxidative stress) are increased >2.5 fold in 9-week old mutants (J:113016)

cardiovascular system
• heart muscle shows pronounced myofibrillar fragmentation and disorganization and increased number of mitochondria (J:113016)
• individual cardiomyocytes are markedly increased in size (J:113016)
• mice have grossly enlarged hearts at 9 weeks of age (J:113016)
• 9-week old mice show significant increase in heart weight/tibial-length ratios (J:113016)
• mutants display severe dilated cardiomyopathy (J:113016)
• detectable by 4 weeks of age and progressively worsens (J:113016)
• significant decrease is shown by decreased percentage fractional shortening, decreased velocity of circumferential fiber shortening and reduced peak aortic outlflow velocity (J:113016)
• also, dP/dTmax and dP/dTmin are reduced significantly (J:113016)
• mutants have significant decrease in ventricular blood pressures (J:113016)

muscle
• heart muscle shows pronounced myofibrillar fragmentation and disorganization and increased number of mitochondria (J:113016)
• individual cardiomyocytes are markedly increased in size (J:113016)
• mutants display severe dilated cardiomyopathy (J:113016)
• detectable by 4 weeks of age and progressively worsens (J:113016)
• significant decrease is shown by decreased percentage fractional shortening, decreased velocity of circumferential fiber shortening and reduced peak aortic outlflow velocity (J:113016)
• also, dP/dTmax and dP/dTmin are reduced significantly (J:113016)
• myofibers from 3-month old mice display irregular contours (J:113016)
• myofiber cross-sectional area is reduced 2-fold in triceps of 3 month old mice vs littermate controls (J:113016)
• male hemizygotes display significant loss of muscle mass at 3 months, becoming detectable at 10 weeks of age compared to littermate controls (Pdcd8-sufficent and non-transgenic hemizygotes) (J:113016)
• muscle degeneration is progressive, becoming detectable at 10 weeks of age; it is most apparent in fast-twitch muscles (gastrocnemium, triceps, quadriceps) (J:113016)
• all skeletal muscles analyzed including triceps, pectoralis, quadriceps, gluteus, and gastrocnemius muscles are significantly atrophied male hemizygotes (J:113016)

homeostasis/metabolism
• plasma lactate levels increase progressively with muscle loss (J:113016)
• a significant increase in lactate/pyruvate ratio is observed (J:113016)
• mutant cardiomyocytes undergo compensatory metabolic switch toward glycolysis, and away from pyruvate utilization as result of impaired mitochondrial respiration (J:113016)
• mutants show significant upregulation of atrial naturietic factor (ANF) and b-type natruietic peptide (BNP) (J:113016)
• at 4.5 months of age, heart and skeletal muscle show significant reductions in catalase activity (J:113016)

behavior/neurological
• loss of muscle mass results makes mice extremely lethargic by 5 months of age (J:113016)


Mouse Genome Informatics
cn20
    Pdha1tm1Ptl/Y
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• when weaned onto rodent laboratory chow, male mice die 7 days after weaning (J:141289)
• when mice are weaned onto a high fat diet, male mice die 12 days after switching from a high fat diet to rodent laboratory chow (J:141289)

cardiovascular system
• compared to in heterozygous female mice and wild-type mice (J:141289)
• whether mice are fed a high fat or laboratory chow diet, the left ventricular diastolic dimension is increased compared to in wild-type mice (J:141289)
• whether fed a high fat or laboratory chow diet, mice exhibit reduced fractional shortening compared to in heterozygous female mice and wild-type mice (J:141289)

homeostasis/metabolism

growth/size
• at 9 weeks of age (J:141289)

muscle
• compared to in heterozygous female mice and wild-type mice (J:141289)
• whether fed a high fat or laboratory chow diet, mice exhibit reduced fractional shortening compared to in heterozygous female mice and wild-type mice (J:141289)


Mouse Genome Informatics
cn21
    Pdha1tm1Ptl/Pdha1+
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• mice exhibit increased heart weight compared to in wild-type mice (J:141289)
• however, heart weight to body weight is normal (J:141289)
• when mice are transitioned from a high fat diet to a rodent laboratory diet, the left ventricular diastolic dimension is increased compared to in wild-type mice (J:141289)
• when transitioned from a high fat diet to a rodent laboratory diet, mice exhibit reduced fractional shortening compared to in wild-type mice (J:141289)

growth/size
• at 9 weeks of age (J:141289)

homeostasis/metabolism

muscle
• when transitioned from a high fat diet to a rodent laboratory diet, mice exhibit reduced fractional shortening compared to in wild-type mice (J:141289)


Mouse Genome Informatics
cn22
    Glultm3Whla/Glultm1Whla
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 20% reduction in plasma glutamine in starved mice
• muscle glutamine20-30% lower
• 35% increase in branched-chain amino acids
• detoxification of ammonia is two fold lower

growth/size
• faster weight loss when fasting but only for the first 20 hours


Mouse Genome Informatics
cn23
    Glultm3Whla/Glultm3Whla
Tg(Ckmm-cre)5Khn/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• faster weight loss when fasting but only for the first 20 hours

homeostasis/metabolism
• 20% reduction in plasma glutamine in starved mice
• muscle glutamine20-30% lower
• 35% increase in branched-chain amino acids
• detoxification of ammonia is two fold lower


Mouse Genome Informatics
cn24
    Pnpla2tm1Eek/Pnpla2tm1Eek
Tg(Ckmm-cre)5Khn/0

involves: 129S * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system

homeostasis/metabolism
• 10.7-fold in cardiac muscle


Mouse Genome Informatics
cn25
    Srftm2.1Nor/Srftm2.1Nor
Tg(Ckmm-cre)5Khn/0

involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Severe runting and skeletal muscle abnormalities in Srftm2.1Nor/Srftm2.1Nor Tg(Ckmm-cre)5Khn/0 mice

mortality/aging
• mutants are born alive and are able to feed but die by P7

behavior/neurological
• starts around P3

growth/size
• starts around P3

muscle
• at P3 myofibers are thinner than normal; however, no cardiac abnormalities are seen
• less severe than in homozygous Srf conditional mutants hemizygous for Tg(Myog-cre)1Eno


Mouse Genome Informatics
cn26
    Fktntm1Kcam/Fktntm1Kcam
Tg(Ckmm-cre)5Khn/?

involves: 129S/SvEv * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• signs of dystrophic disease at 12 weeks of age
• central nucleation in muscle fibers
• variable fiber size
• hypercontracted fibers

homeostasis/metabolism
• elevated serum creatine kinase at 12 weeks of age

behavior/neurological
• reduced running times on a treadmill


Mouse Genome Informatics
cn27
    Erbb2tm3(Erbb2)Mul/Erbb2tm3(Erbb2)Mul
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * BALB/c * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• early mortality is observed in severely affected mutants

behavior/neurological
• loss of coordination
• progressive with age, animals rest on abdomen instead of limbs
• mutants often maintain limbs in an abnormal posture, progressing from a flexor to an extensor posture
• progressive with age

craniofacial

growth/size

muscle
• an increase in apoptosis is observed in mutant myoblasts infected with adenoviral-cre (to completely obliterate expression) during induced differentiation
• muscle fibers that regenerate after injury are not continuous and are interspersed with encapsulated cellular debris

skeleton

nervous system


Mouse Genome Informatics
cn28
    Mterf4tm1.1Lrsn/Mterf4tm1.1Lrsn
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• maximal life span is shortened to 21 weeks

cardiovascular system
• gradual accumulation of mitochondria with abnormal morphology in the myocardium from 5 weeks of age onwards
• gradual increase in absolute and relative heart size with age
• levels of assembled complexes containing mtDNA-encoded subunits are decreased from 5 weeks of age onward
• severe respiratory chain deficiency
• severe mitochondrial cardiomyopathy develops from 5 weeks of age onwards

cellular
• severe decrease of in organello translation in the hearts

growth/size
• from 15 weeks of age

muscle
• gradual accumulation of mitochondria with abnormal morphology in the myocardium from 5 weeks of age onwards
• severe mitochondrial cardiomyopathy develops from 5 weeks of age onwards


Mouse Genome Informatics
cn29
    Mterf3tm1.1Lrsn/Mterf3tm1.1Lrsn
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die by 18 weeks of age

cardiovascular system
• mice exhibit an increase in relative mitochondrial mass in hearts unlike in wild-type mice
• mice exhibit a gradual increase in heart size with abnormal mitochondria unlike in wild-type mice
• mitochondrial

cellular
• steady-state mitochondrial transcription is decreased compared to in wild-type cells
• the enzymatic activity of all mitochondrial complexes in heart tissues is decreased compared to in wild-type mice

growth/size
• at 16 weeks of age

muscle
• mice exhibit an increase in relative mitochondrial mass in hearts unlike in wild-type mice
• mitochondrial


Mouse Genome Informatics
cn30
    Tfb1mtm1.1Lrsn/Tfb1mtm1.1Lrsn
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• at 24 weeks of age

cardiovascular system
• after 10 weeks, mitochondrial mass in cardiomyocytes increases unlike in wild-type mice
• after 15 weeks
• at 15 to 20 weeks, mitochondrial biogenesis in cardiomyocytes is increased compared to in wild-type mice
• at 5 and 20 weeks, respiratory function and mitochondrial ATP production is decreased compared to in wild-type cells
• heart cells exhibit increased mitochondrial transcription but decreased translation compared to in wild-type cells

muscle
• after 10 weeks, mitochondrial mass in cardiomyocytes increases unlike in wild-type mice


Mouse Genome Informatics
cn31
    Hif1atm3Rsjo/Hif1atm3Rsjo
Tg(Ckmm-cre)5Khn/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• increase in muscle damage following exercise

homeostasis/metabolism
• increased serum levels of the MM isoform of creatine kinase 1 day after exercise
• significant decrease in lactate accumulation after exercise
• increased endurance in swim tests and in the first session of running uphill (concentric exercise) but decreased endurance when running downhill (eccentric exercise)
• endurance decreased over 4 consecutive days of daily treadmill running

nervous system
• slight but statistically significant decrease in type IIa fibers in the soleus


Mouse Genome Informatics
cn32
    Mstntm1Mgs/Mstntm1Mgs
Tg(Ckmm-cre)5Khn/?

involves: 129S1/Sv * 129X1/SvJ * CD-1 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• mutants weigh 23% and 26% more than controls at 2 months and 5 months of age, respectively

muscle
• generalized muscle hypertrophy, resulting in a 'double-muscling' phenotype
• superficial muscle layers exhibit a more severe hypertrophy than the deep layers


Mouse Genome Informatics
cn33
    Dag1tm2Kcam/Dag1tm2Kcam
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• at ~6 weeks, mutant skeletal muscles show loss of dystrophin, dystrobrevin, and the sarcoglycan-sarcospan complex
• during cycles of degeneration, satellite cells are repetitively activated leading to expression of dystroglycan and other components of the DGC in muscle fibers undergoing regeneration
• surprisingly, aging mutants develop marked hypertrophy of skeletal muscle fibers
• a >2-fold increase in fiber diameter of the quadriceps and soleus muscle noted at 18 months
• at ~6 weeks, mutant mice show variation of skeletal muscle fiber size
• up to 95% of skeletal muscle fibers exhibit centrally located nuclei
• at 15 months, mutants show a widespread increase in wet muscle weight, esp. in the quadriceps and gastrocnemius muscles, where the weight is doubled
• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis
• at ~6 weeks, mutants exhibit hallmarks of muscular dystrophy, such as myonecrosis, central nucleation, and variation of fiber size
• however, despite ongoing cycles of muscle degeneration, aging mutants exhibit only a mild dystrophy with signs of efficient muscle regeneration and marked skeletal muscle hypertrophy but no signs of fibrosis or fat replacement

homeostasis/metabolism
• mutant mice exhibit significant elevation of serum creatine kinase levels

growth/size
• at 15 months, mutant mice are significantly larger than control littermates


Mouse Genome Informatics
cn34
    Rr27tm1Kpfe/Rr27tm1Kpfe
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• maternal allele imprinting is lost
• however, imprinting at the H19 promoter in the paternal allele is normal


Mouse Genome Informatics
cn35
    Lrpprctm1.1Lrsn/Lrpprctm1.1Lrsn
Tg(Ckmm-cre)5Khn/0

involves: 129S1/Sv * 129X1/SvJ * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die before 16 weeks of age

cellular
• increased mitochondrial DNA content
• increased mitochondrial mass associated with a severe cytochrome c oxidase deficiency
• severe cytochrome c oxidase deficiency
• aberrant polyadenyation of mitochondrial mRNA and impaired mRNA stability

cardiovascular system


Mouse Genome Informatics
cn36
    Scyl1tm1Spel/Scyl1tm1Spel
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice exhibit normal gait and motor function (J:192445)

muscle
N
• mice exhibit normal gait and motor function (J:192445)

nervous system
N
• mice exhibit nor signs of neuroinflammation or neurodegeneration (J:192445)


Mouse Genome Informatics
cn37
    Insrtm1Khn/Insrtm1Khn
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• heart function and morphology is normal (J:118987)

growth/size
N
• mice exhibit normal growth rates (J:118987)

homeostasis/metabolism
N
• mice exhibit normal glucose homeostasis (J:118987)


Mouse Genome Informatics
cn38
    Dgcr8tm1.1Blel/Dgcr8tm1.1Blel
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die before 2 months of age and median survival is 31 days

cardiovascular system
• at 4 weeks, mice exhibit increased end-diastolic and end-systolic diameters compared with wild-type mice
• in the left and right ventricular wall
• in the ventricular wall at 3 weeks
• at 3 weeks, mice exhibit loss of ventricular function unlike wild-type mice
• at 4 weeks, fractional shortening is reduced in the ventricle compared with wild-type mice
• increased in width

muscle
• at 3 weeks, mice exhibit loss of ventricular function unlike wild-type mice
• at 4 weeks, fractional shortening is reduced in the ventricle compared with wild-type mice


Mouse Genome Informatics
cn39
    Mapk8tm1Jcbr/Mapk8tm1Jcbr
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
N
• whether fed standard chow or a high fat diet, mice exhibit normal body composition (J:195844)

homeostasis/metabolism
N
• whether fed standard chow or a high fat diet, mice exhibit normal energy homeostasis, insulin sensitivity and glucose homeostasis (J:195844)


Mouse Genome Informatics
cn40
    Insrtm1Khn/Insrtm1Khn
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• larger than normal fat depots in fat pads, including the perianal, subcutaneous and perigonadal fat pads

homeostasis/metabolism
N
• normal serum cholesterol levels (J:51266)
• normoglycemia, up to 11 months of age (J:51266)
• normal glucose tolerance (J:51266)
• normal concentrations of serum insulin (J:51266)
• 20% elevation in serum free fatty acids (FFAs)
• greater than70% elevated, observed from ages 4 to 11 months


Mouse Genome Informatics
cn41
    Insrtm1Khn/Insrtm1Dac
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in the fed state, incomplete penetrance


Mouse Genome Informatics
cn42
    Akt1tm2Mbb/Akt1tm2Mbb
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
N
• mice do not phenocopy knock-out mice (J:182721)

homeostasis/metabolism
N
• mice do not phenocopy knock-out mice (J:182721)


Mouse Genome Informatics
cn43
    Slc2a4tm1Abel/Slc2a4tm1Abel
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• during a 2 hour hyperinsulinemic-euglycemic clamp insulin-stimulated whole body glycolysis is reduced by 59% (49 umol/kg/min vs 118 umol/kg/min in 21-week old controls)
• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated whole body glycolysis is reduced by 43% (95 umol/kg/min vs 166 umol/kg/min in young controls)
• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated skeletal muscle glycolysis is reduced by 92% (18 nmol/g/min vs 223 nmol/g/min in young controls)
• in young mutants treated from 12 weeks of age with phloridzin, whole body glycolysis is reduced by 30% (98 vs 118 umol/kg/min) and and muscle glycolysis is reduced by 82% (44 vs 251 nmol/g/min); hepatic glucose production is unaffected by insulin
• during a 2 hour hyperinsulinemic-euglycemic clamp inhibition of hepatic glucose production by mutants is impaired in 21-week old mutants
• basal plasma glucose concentration (8.2mM) is increased about 20% compared to controls (Slc2a4tm1Abel homozygotes at 21 weeks of age or mice expressing Tg(Ckmm-cre)1Khan alone) where levels are 6.8-7.2 mM
• however, young (0-week old) muscle-specific knockouts showed no increased plasma glucose vs age-matched controls
• in young mutants treated from 12 weeks of age with phloridzin, plasma glucose levels show an initial increase (10.2 vs 6.7 mM in controls) but levels gradually decrease to comparable levels with controls (8.2, 6.9 and 7.0 mM vs 7.0 mM in controls at 14, 17 and 20 weeks of age)
• 21-week old knockout mice do not show differences in basal plasma insulin levels after an overnight fast, while levels are significantly increased in young (10-week old) knockouts (~110 pM vs 53 pM) and phloridzin treated knockouts compared to their respective controls (166 pM vs 86 pM)
• during a 2 hour hyperinsulinemic-euglycemic clamp insulin-stimulated whole body glycogen/lipid synthesis is decreased by 50% in 21-week old knockouts
• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated whole body glycogen/lipid synthesis is decreased by 60% (36 vs 90 umol/kg/min) compared to young controls
• during a 2 hour hyperinsulinemic-euglycemic clamp,in 10-week old mutants insulin-stimulated skeletal muscle glycogen/lipid synthesis is decreased by 89% (0.7 vs 2.7 nmol/g/min) compared to young controls
• in young mutants treated from 12 weeks of age with phloridzin, whole body glycogen/lipid biosynthesis is decreased by 36% (44 vs 106 umol/kg/min) and muscle glycogen/lipid synthesis is reduced by 45% ( 4.7 vs 8.7 nmol/g/min)

muscle
• uptake in skeletal (gastrocnemius) muscle is decreased by 92% in muscle-specific knockouts (20 vs 237 nmol//g/min in controls)
• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated uptake in skeletal muscle in 10-week old mutants is decreased by 85% (39 vs 261 nmol/g/min in young controls)
• in young mutants treated from 12 weeks of age with phloridzin, skeletal uptake is decreased by 81% (49 vs 227 nmol/g/min)

adipose tissue
• insulin-stimulated glucose in white adipose tissue and intracapsular brown adipose tissue is decreased by 69% (9 nmol/g/min vs 28 nmol/g/min) and 84%(37 nmol/g/min vs 237 nmol/g/min) respectively
• in 10 week old mutants insulin-stimulated uptake is increased 2-fold in white adipose tissue 26 vs 13 nmol/g/min) and brown adipose tissue (453 vs 224 nmol/g/min) compared to young controls
• in young mutants treated from 12 weeks of age with phloridzin, insulin-stimulated uptake in brown adipose tissue is increased (633 vs 247 nmol/g/min) but is unchanged in white adipose tissue

digestive/alimentary system
• in 21-week old mutants during a 2 hour hyperinsulinemic-euglycemic clamp insulin stimulated whole body uptake is decreased by 55% in muscle-specific knockout mice (102 umol/kg/min vs 224 umol/kg/min)
• during a 2 hour hyperinsulinemic-euglycemic clamp, insulin-stimulated whole body uptake in 10-week old mutants is decreased by 49% (130 vs 256 nmol/g/min in young controls)
• in young mutants treated from 12 weeks of age with phloridzin, whole body uptake is decreased by 32% (142 vs 224 umol/kg/min)


Mouse Genome Informatics
cn44
    Slc2a4tm1Abel/Slc2a4+
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• insulin stimulated muscle uptake is decreased in heterozygous muscle-specific knockout mice

digestive/alimentary system
• insulin stimulated whole body uptake is decreased in heterozygous muscle-specific knockout mice
• i


Mouse Genome Informatics
cn45
    Ptentm1Hwu/Ptentm1Hwu
Tg(Ckmm-cre)5Khn/?

involves: 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• in mice fed a normal diet, the weights of injured tibialis anterior muscles are greater than weights of muscles in controls
• regenerating myofibers after injury are larger compared to control injured myofibers, indicating that mutants exhibit a promotion in regeneration of injured muscles
• after 8 months of a high-fat diet, mutants exhibit larger myofiber sizes of regenerating muscles at 6 and 12 days after injury and increased weights of the injured tibialis anterior muscles than controls
• after 8 months on a high-fat diet, collagen deposition is reduced in regenerating muscles compared to controls

homeostasis/metabolism
• after 8 months of a high-fat diet, mutants exhibit lower glucose levels than controls on the same diet
• after 8 months of a high-fat diet, mutants exhibit lower insulin levels than controls on the same diet


Mouse Genome Informatics
cn46
    Pik3r1tm1Lca/Pik3r1tm1Lca
Tg(Ckmm-cre)5Khn/0

involves: 129S6/SvEvTac * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mutants are viable and fertile, with no gross abnormalities and normal muscle morphology


Mouse Genome Informatics
cn47
    Pik3r1tm1Lca/Pik3r1tm1Lca
Pik3r2tm1Lca/Pik3r2tm1Lca
Tg(Ckmm-cre)5Khn/0

involves: 129S6/SvEvTac * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• most cardiomyocytes are reduced in size
• heart size normalized to body weight or tibia length is about 20% smaller than in wild-type mice; however the structure of the heart is normal with no obvious signs of fibrosis or tissue damage
• the increase in heart size in response to exercise is decreased compared to wild-type mice

muscle
• most cardiomyocytes are reduced in size


Mouse Genome Informatics
cn48
    Aplp2tm1Dbo/Aplp2tm1Dbo
Apptm1.1Zhe/Apptm1.1Zhe
Tg(Ckmm-cre)5Khn/0

involves: 129S7/SvEvBrd * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E16.5, endplate band width and number are increased compared to in wild-type mice that is as severe as in Aplp2tm1Dbo Apptm1.2Zhe double homozygotes
• at P0, presynaptic and postsynaptic terminal distribution is diffuse and nerve terminal sprouting occurs unlike in wild-type that is as severe as in Aplp2tm1Dbo Apptm1.2Zhe double homozygotesmice


Mouse Genome Informatics
cn49
    Fkbp1atm1Zuk/Fkbp1atm1Slh
Tg(Ckmm-cre)5Khn/0

involves: 129S7/SvEvBrd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• males at 3 months of age started to weigh less (26.3 g) than wild-type (31.9 g), while females had similar weights

muscle
• mRNAs for all three isoforms of calcineurin A are significantly elevated in the diaphragm muscle; a significant increase in calcineurin protein levels is seen in diaphragm muscle homogenates from the mutant mice.
• no difference observed in calcineurin protein level in EDL and soleus muscles between mutant mice and controls
• the diaphragm exhibits an increased percentage of muscle fibers containing internal nuclei
• the diaphragm muscle shows a shift in fast to slow muscle fiber ratio (i.e. of type I to type II fibers)
• mutant myotubes exhibit a reduced maximal voltage-gated Ca2+ release, but decay of the Ca2+transients is not significantly different in the mutant and control
• mutant myotubes were more sensitive to caffeine-induced Ca2+ release than controls
• no significant differences in resting Ca2+ levels
• greater tetanic force in the diaphragm than in controls at frequencies between 15 and 50 Hz; however, isometric tetanic force in the extensor digitorum longus (EDL) muscles was 19-32% less than controls at stimulation frequencies between 60 and 300 Hz
• abnormal calcium homeostasis

homeostasis/metabolism
• mutant myotubes exhibit a reduced maximal voltage-gated Ca2+ release, but decay of the Ca2+transients is not significantly different in the mutant and control
• mutant myotubes were more sensitive to caffeine-induced Ca2+ release than controls
• no significant differences in resting Ca2+ levels


Mouse Genome Informatics
cn50
    Fkbp1atm1Slh/Fkbp1atm1Slh
Tg(Ckmm-cre)5Khn/0

involves: 129S7/SvEvBrd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• muscles exhibit increased abnormal mitochondrial compared with wild-type muscles
• extensor digitorum longus muscle-specific force and action potential-triggered calcium transient amplitudes are reduced compared to in wild-type muscles
• muscles exhibit leaky calcium channels indicated by enhanced frequency of calcium sparks compared with wild-type mice
• muscles exhibit S107-resistant oxidative stress unlike wild-type muscles
• S107-treatment does not improve abnormal muscle physiology
• extensor digitorum longus muscle-specific force is reduced compared to in wild-type muscles

homeostasis/metabolism

cellular
• S107-resistant oxidative stress in muscles

behavior/neurological


Mouse Genome Informatics
cn51
    Fkbp1atm1.1Shou/Fkbp1atm1Zuk
Tg(Ckmm-cre)5Khn/0

involves: 129S7/SvEvBrd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• cardiac development appears normal (J:195489)


Mouse Genome Informatics
cn52
    Pdpk1tm1.1Mlw/Pdpk1tm1.1Mlw
Tg(Ckmm-cre)5Khn/?

involves: BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• normal numbers born
• normal phenotype and survive to wk 5
• growth normal
• breathe and eat normally
• normal activity
• not diabetic to wk 8
• all die at age 5-11 wks
• drop in activity 2-3 days before death and weight loss
• noncardiac muscle normal

cardiovascular system
• by 6 wks, collagen levels, ANF and beta-myosin heavy chain levels are increased in hearts
• increased sensitivity of cardiomyocytes to hypoxia
• atria enlarge by 6 wks and massively inflated at death
• cardiomyocytes appear more separated from each other
• reduction in cardiomyocyte volume
• muscle mass of hearts is significantly reduced
• from 2-4 weeks, hearts became progressively smaller in relative terms but otherwise were normal
• by 6 weeks hearts were much smaller with reduced muscle mass due to smaller cardiomyocytes
• right ventricle is significantly enlarged by 6 weeks of age
• by 6 weeks
• extremely thin by death
• by 8 weeks of age, exhibit an increase in Z-line thickness, a feature of dilated cardiomyopathy
• echocardiograms at 5-6 weeks revealing development of heart failure
• reduced fractional shortening and ejection fraction

growth/size
• observe a significant reduction in body weight 2-3 days before mutants die

muscle
• cardiomyocytes appear more separated from each other
• reduction in cardiomyocyte volume
• by 8 weeks of age, exhibit an increase in Z-line thickness, a feature of dilated cardiomyopathy
• reduced fractional shortening and ejection fraction
• thicker Z-line by 8 weeks of age


Mouse Genome Informatics
cn53
    Cfl2tm1Itl/Cfl2tm1Itl
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * C57BL/6NTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice live for 16 to 33 days
• mice live for 16 to 33 days

muscle
• dissolving
• accumulation of F-actin
• at P21, mice exhibit ballooning degeneration interspersed with normal-looking myofibers and pale core-like areas consistent with myofibrillar disruption and absent mitochondria unlike in wild-type mice

growth/size
• 2- to 4-fold between P8 and P31


Mouse Genome Informatics
cn54
    Txniptm1Road/Txniptm1Road
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal viability (J:132756)

homeostasis/metabolism

reproductive system
N
• mice exhibit normal reproduction (J:132756)

growth/size
N
• mice exhibit normal growth (J:132756)


Mouse Genome Informatics
cn55
    Lig3tm1.1Pmc/Lig3tm1.1Pmc
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 3.5 and 4.5 weeks of age

cardiovascular system
• with abnormal mitochondria
• mice exhibit decreased diastolic and systolic movements of the left ventricle wall and interventricular septum compared with wild-type mice
• fractional shortening and ejection fraction are decreased compared to in wild-type mice

muscle
• with abnormal mitochondria
• fractional shortening and ejection fraction are decreased compared to in wild-type mice


Mouse Genome Informatics
cn56
    Prkab1tm1Grst/Prkab1tm1Grst
Prkab2tm1Grst/Prkab2tm1Grst
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• decrease in intermyofibrillar mitochondrial content
• mitochondria in both the intermyofibrillar and subsarcolemmal regions are larger
• decreased glucose uptake during exercise
• isolated EDL muscles fatigue rapidly

behavior/neurological
• decrease in voluntary wheel activity
• exercise intolerant and have dramatic reductions in both maximal running speed and distance covered

homeostasis/metabolism
• exercise intolerant and have dramatic reductions in both maximal running speed and distance covered
• elevated serum glucose following exercise
• decrease in citrate synthase and cytochrome c oxidase activities


Mouse Genome Informatics
cn57
    Prkab2tm1Grst/Prkab2tm1Grst
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• about a 25% reduction in running capacity

behavior/neurological
• about a 25% reduction in running capacity


Mouse Genome Informatics
cn58
    Gt(ROSA)26Sortm1(CAG-MAP2K7*/MAPK8,-EGFP)Ftw/Gt(ROSA)26Sor+
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
N
• mice exhibit normal body composition (J:195844)

homeostasis/metabolism
N
• mice exhibit normal energy homeostasis, insulin signaling and glucose homeostasis (J:195844)


Mouse Genome Informatics
cn59
    Peo1tm1.1Lrsn/Peo1tm1.1Lrsn
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die at 19 weeks

cardiovascular system
• mice show signs of progressive heart enlargement from age of 8 weeks

cellular
• severe depletion of mitochondrial DNA (mtDNA) is observed in heart-specific mutants; this results in decrease of mtDNA-encoded transcripts and mtDNA-encoded proteins like Cox1 and Cox2
• in heart tissue, levels respiratory complexes and superassemblies containing mtDNA-encoded subunits are decreased complared to an exclusively nucleus-encoded complex indicating that the mutation results in defective respiratory chain assembly in heart mitochondria


Mouse Genome Informatics
cn60
    Fktntm3.1Ttd/Fktntm3.1Ttd
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• exercised mice exhibit increased membrane-impermeable Evans blue dye uptake compared with cells from control mice
• at 16 weeks, increasing with age
• at 16 weeks
• at 16 weeks with myonecrosis and central nucleation

homeostasis/metabolism
• at 16 weeks
• after forced exercise


Mouse Genome Informatics
cn61
    Atf4tm1.1Cmad/Atf4tm1.1Cmad
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• mice exhibit normal skeletal muscle development (J:206503)
• following fasting or 3 days of immobilization
• however, muscular atrophy following 7 days of immobilization is normal


Mouse Genome Informatics
cn62
    Musktm1Vwi/Musktm1Vwi
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die before P30

muscle
• at around 2 to 3 weeks of age, develop severe muscle weakness with impaired mobility and difficulty breathing, eating, and drinking

nervous system
• in older mice, phrenic nerve innervation is seen outside the central band of the diaphragm muscle
• from P20 on, endplates in the diaphragm show decreased acetylcholine receptor densities and begin to disintegrate
• after P20 neuromuscular junction endplates are seen outside the central band where they are normally confined

behavior/neurological
• grip strength from P12 onwards does not increase, unlike in wild-type mice

growth/size
• normal weight gain until about 3 to 4 weeks of age then weight gain stops and weight loss is seen

skeleton


Mouse Genome Informatics
cn63
    Musktm1Vwi/Musktm1.1Vwi
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die before P30

muscle
• at around 2 to 3 weeks of age, develop severe muscle weakness with impaired mobility and difficulty breathing, eating, and drinking

nervous system
• in older mice, phrenic nerve innervation is seen outside the central band of the diaphragm muscle
• from P20 on, endplates in the diaphragm show decreased acetylcholine receptor densities and begin to disintegrate
• after P20 neuromuscular junction endplates are seen outside the central band where they are normally confined

behavior/neurological
• grip strength from P12 onwards does not increase, unlike in wild-type mice

growth/size
• normal weight gain until about 3 to 4 weeks of age then weight gain stops and weight loss is seen

skeleton


Mouse Genome Informatics
cn64
    Crattm1.1Pbrc/Crattm1.1Pbrc
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• gain more weight and more fat mass when placed on a high fat diet
• on a low fat diet body weight and fat mass are similar to wild-type
• both at baseline and throughout an intraperitoneal glucose tolerance test
• exacerbated on a high fat diet
• glucose intolerant
• exacerbated on a high fat diet

cellular
• when pyruvate is the only carbon source addition of carnitine fails to increase state 3 respiration
• rates of CO2 production are increased in isolated muscle mitochondria when exposed to moderate or high concentrations of palmitate
• increase in whole body carbohydrate oxidation in response to an insulin challenge or during the fasting-to-fed transition is diminished
• in isolated skeletal muscle mitochondria there is a near-complete loss of acyltransferase activity using various short chain acyl-CoA substrates

muscle
• impaired efflux of pyruvate dehydrogenase-derived acetylcarnitine from skeletal muscle
• marked accumulation of several medium and long chain acylcarnitines in skeletal muscle and to a lesser degree in the heart

cardiovascular system
• several short, medium, and long chain acyl-CoA species are elevated in the heart

growth/size
• gain more weight and more fat mass when placed on a high fat diet
• on a low fat diet body weight and fat mass are similar to wild-type


Mouse Genome Informatics
cn65
    Pik3c3tm1c(EUCOMM)Wtsi/Pik3c3tm1c(EUCOMM)Wtsi
Tg(CAG-EGFP/Map1lc3b)53Nmz/0
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6N * C57BL/6NCrj * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• hearts from fed and starved exhibit blocked autophagy flux compared with control hearts

cellular
• hearts from fed and starved exhibit blocked autophagy flux compared with control hearts


Mouse Genome Informatics
cn66
    Pik3c3tm1c(EUCOMM)Wtsi/Pik3c3tm1c(EUCOMM)Wtsi
Tg(Ckmm-cre)5Khn/0

involves: C57BL/6N * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cardiac dysfunction in Pik3c3tm1c(EUCOMM)Wtsi/Pik3c3tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0 mice

mortality/aging
• mice die between 5 and 13 weeks of age

cardiovascular system
• hearts exhibit disorganized mitochondria and Z-lines with increased number of small-sized mitochondria and enlarged vacuoles compared with control hearts
• mice exhibit an increased in left ventricular wall thickness and mass compared with control mice
• decreased cardiac contractility with lower ejection fraction and fractional shortening compared with control mice

muscle
• decreased cardiac contractility with lower ejection fraction and fractional shortening compared with control mice


Mouse Genome Informatics
cn67
    Stk11tm1Keis/Stk11tm1Keis
Tg(Ckmm-cre)5Khn/0

involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• block of glucose uptake stimulated by 5-aminoimidazole-4-caroboxamide (AICAR) or by muscle contraction, but not by insulin
• possessed normal fasted and fed blood glucose levels

reproductive system
• homozygous male mice are infertile, female are fertile (J:98513)

growth/size
N
• normal growth from 4 to 10 weeks of age (J:98513)


Mouse Genome Informatics
cn68
    Plrg1tm2Jcbr/Plrg1tm2Jcbr
Tg(Ckmm-cre)5Khn/0

involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival at P28 is 5% compared to 80% for wild-type mice

cardiovascular system
• at P24, both ventricles exhibit atrophy unlike in wild-type mice

muscle

cellular


Mouse Genome Informatics
cn69
    Ttntm1Her/Ttntm1Her
Tg(Ckmm-cre)5Khn/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death at about 5 wks of age

behavior/neurological

cardiovascular system
N
• the heart was reduced in size, but in proportion to reduced overall body size (J:81993)
• no pathology of the heart was reported (J:81993)

growth/size
• apparent at 3 wks of age

muscle
• pale, widened M-lines, devoid of M-line bridges
• disarrayed sarcomeres, observed in less than 50% of the area of the myocytes
• resulting in abnormal posture, gait, and blepharoptosis

vision/eye

Mouse Models of Human Disease
OMIM IDRef(s)
Muscular Dystrophy, Limb-Girdle, Type 2J; LGMD2J 608807 J:81993