Mouse Genome Informatics
cn1
    Myl1tm1(cre)Sjb/Myl1+
Shc1tm9Paw/Shc1tm9Paw

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• all viable mice are severely uncoordinated, appearing similar to Shc1tm4Paw homozygotes

nervous system
• between P22 and P35, muscle spindle numbers are reduced 50% compared to controls
• intrafusal fiber numbers are 59% that of controls

muscle
• between P22 and P35, muscle spindle numbers are reduced 50% compared to controls
• intrafusal fiber numbers are 59% that of controls


Mouse Genome Informatics
cn2
    Myl1tm1(cre)Sjb/Myl1+
Shc1tm3Paw/Shc1tm9Paw

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• motor abnormalities are similar to those observed in Shc1tm7Paw homozygotes

nervous system
• between P22 and P35, muscle spindle and intrafusal fiber numbers are reduced compared to controls

muscle
• between P22 and P35, muscle spindle and intrafusal fiber numbers are reduced compared to controls


Mouse Genome Informatics
cn3
    Myl1tm1(cre)Sjb/Myl1+
Shc1tm4Paw/Shc1tm9Paw

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• motor abnormalities are less severe, similar to those observed in Shc1tm4Paw homozygotes

muscle
• between P22 and P35, intrafusal fiber numbers are reduced compared to controls

nervous system
• between P22 and P35, intrafusal fiber numbers are reduced compared to controls


Mouse Genome Informatics
cn4
    Myl1tm1(cre)Sjb/Myl1+
Shc1tm7Paw/Shc1tm9Paw

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• motor abnormalities are similar to those observed in Shc1tm7Paw homozygotes

muscle
• between P22 and P35, muscle spindle and intrafusal fiber numbers are reduced compared to controls

nervous system
• between P22 and P35, muscle spindle and intrafusal fiber numbers are reduced compared to controls


Mouse Genome Informatics
cn5
    Myl1tm1(cre)Sjb/Myl1+
Tfamtm1Lrsn/Tfamtm1Lrsn

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Skeletal muscle analysis of Tfamtm1Lrsn/Tfamtm1Lrsn Myl1tm1(cre)Sjb/Myl1+ mice

mortality/aging
• death occurs at 4-5 months of age

muscle
• increased muscle fiber size containing enlarged mitochondria with distorted cristae
• shorter contraction times and shorter twitch-relaxation times
• decreased absolute muscle force

cellular
• respiratory chain dysfunction in skeletal muscle

behavior/neurological
• from 3-4 months of age

growth/size/body
• beginning at 4-5 months of age


Mouse Genome Informatics
cn6
    Cox10tm1Ctm/Cox10tm1Ctm
Myl1tm1(cre)Sjb/Myl1+

involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant mice have a shorter life span
• females died younger than males

muscle
• showed areas of mitochondrial proliferation and markedly enlarged and swollen mitochondria
• no signs of fibrosis, inflammation, or apoptosis were seen
• mutant muscle fibers are more heterogeneous in size
• at 3-4 months of age, severe reductions in muscle mass are seen
• maximal force evoked in mutant muscle is significantly smaller
• the muscles from mutant mice are more fatigable than control
• mutant mice are healthy until approximately 3 months of age then develop a slowly progressive myopathy
• the myopathy starts earlier and worsens quicker in female

growth/size/body
• at 3-4 months of age, they started to lose weight
• female mutant mice weigh less at an early age

skeleton
• starting at 3-4 months of age

behavior/neurological
• starting at 3-4 months of age
• in treadmill performance test, 2-month old mutant mice had difficulty in performing the task
• the female performance was significantly poorer than males

Mouse Models of Human Disease
OMIM IDRef(s)
Mitochondrial Myopathy 251900 J:101747