Phenotypes associated with this allele

• Allele Symbol: Calr^tm1Mlk
• Allele Name: targeted mutation 1, Marek Michalak
• Allele ID: MGI:2176266
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Calr^tm1Mlk/Calr^tm1Mlk	involves: 129S4/SvJae * C57BL/6J	MGI:3044183

Genotype
MGI:3044183

hm1

• Allelic Composition: Calr^tm1Mlk/Calr^tm1Mlk
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

Umbilical hernia in Calr^tm1Mlk/Calr^tm1Mlk mice

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:53466 )

• homozygous embryos diplayed mid- to late-gestational lethality

• at or after E14.5, the number of homozygous null embryos decreased to 15% (instead of 25%)

growth/size/body

omphalocele ( J:53466 )

• at E18, mutant embryos displayed omphalocele (failure to absorb the umbilical hernia)

cardiovascular system

increased cardiac muscle glycogen level ( J:119647 )

• glycogen accumulates in the ventricular sarcoplasm of the heart

abnormal myocardial fiber morphology ( J:119647 )

• ventricular myofibrillar disarray is more pronounced in the mutants at E12.5 than in wild-type, however by E18.5, myofibrils attain organization that is similar to wild-type

• ventricular myofibrils are approximately 32% thinner than wild-type at E12.5-E18.5

• thinning of the atrial myofibrils becomes noticeable at the mid- and late (E14.5-E18.5) stages of embryonic development

abnormal intercalated disk morphology ( J:119647 )

• intercalated discs of ventricular myocardial tissue tend to run in a stepwise fashion instead of almost straight lines as in wild-type

decreased myocardial fiber number ( J:119647 )

• ventricular myocardium contains lower numbers of myofibrils at E12.5-E18.5

• myofibrillar count becomes lower in atria at mid (E14.5-E15.5) and late (E16.5-E18.5) stages of development

thin myocardium compact layer ( J:53466 )

• mutant embryos exhibited reduced growth of the compact layer of the ventricles

small heart ( J:119647 )

• embryonic hearts are smaller than in wild-type

trabecula carnea hypoplasia ( J:53466 , J:119647 )

• histology of hearts from 12.5-, 14.5-, and 18-day-old embryos showed deep intertrabecular recesses and increased fenestration in the ventricular walls (J:53466)

• the increase in ventricular trabeculation that is seen in wild-type hearts by E16.5 is not observed in mutant hearts (J:119647)

thin ventricular wall ( J:53466 , J:119647 )

• at E18, mutant embryos displayed a significant reduction in the thickness of ventricular walls (J:53466)

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:119647 )

• glycogen accumulates in the ventricular sarcoplasm of the heart

abnormal calcium ion homeostasis ( J:53466 )

• mutant embryonic fibroblasts show inhibition of InsP3-dependent (bradykinin-induced) Ca²⁺ release from the ER and impaired nuclear import of the NF-AT3 transcription factor, indicating impaired Ca²⁺ homeostasis

muscle

increased cardiac muscle glycogen level ( J:119647 )

• glycogen accumulates in the ventricular sarcoplasm of the heart

abnormal myocardial fiber morphology ( J:119647 )

• ventricular myofibrillar disarray is more pronounced in the mutants at E12.5 than in wild-type, however by E18.5, myofibrils attain organization that is similar to wild-type

• ventricular myofibrils are approximately 32% thinner than wild-type at E12.5-E18.5

• thinning of the atrial myofibrils becomes noticeable at the mid- and late (E14.5-E18.5) stages of embryonic development

abnormal intercalated disk morphology ( J:119647 )

• intercalated discs of ventricular myocardial tissue tend to run in a stepwise fashion instead of almost straight lines as in wild-type

decreased myocardial fiber number ( J:119647 )

• ventricular myocardium contains lower numbers of myofibrils at E12.5-E18.5

• myofibrillar count becomes lower in atria at mid (E14.5-E15.5) and late (E16.5-E18.5) stages of development

trabecula carnea hypoplasia ( J:53466 , J:119647 )

• histology of hearts from 12.5-, 14.5-, and 18-day-old embryos showed deep intertrabecular recesses and increased fenestration in the ventricular walls (J:53466)

• the increase in ventricular trabeculation that is seen in wild-type hearts by E16.5 is not observed in mutant hearts (J:119647)

thin myocardium compact layer ( J:53466 )

• mutant embryos exhibited reduced growth of the compact layer of the ventricles

abnormal sarcomere morphology ( J:119647 )

• significant increase of 35% in sarcomeric angle of myofibrils between E14.5 and E18.5

abnormal Z line morphology ( J:119647 )

• cardiac ventricular Z-lines are not well aligned, even at later stages of development, however atrial Z-lines are normal