Mouse Genome Informatics
hm
    Fkbp1atm1Zuk/Fkbp1atm1Zuk
either: (involves: 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• at E18.5, most homozygotes exhibit rapid demise suggesting perfusion failure
• only a few (8) homozygotes survive to weaning; however, 7 of 8 die within a few weeks because of a cardiac-related wasting syndrome while the eighth one survived to 14 months
• most homozygotes die between E14.5 and birth

cardiovascular system
• at E14.5 and E18.5, most homozygotes exhibit noncompaction of left ventricular myocardium
• at E14.5 and E18.5, homozygotes display hypertrophic trabeculae with deep intertrabecular recesses
• at E14.5 and E18.5, homozygotes exhibit prominent ventral septal defects
• at E18.5, most homozygotes display a significantly increased heart weight relative to wild-type mice (13.4 0.44 mg vs 8.14 0.38 mg)
• at E14.5 and E18.5, homozygotes display a thinner left ventricular wall
• at E18.5, most homozygotes display an enlarged heart due to four-chamber dilation
• homozygotes exhibit severe dilated cardiomyopathy associated with aberrant single-channel gating properties of both skeletal and cardiac ryanodinereceptors
• at E14.5, many homozygotes exhibit severe liver hemorrhage
• a single 14-mo-old homozygote displayed reduced contractile activity in the ventricular wall, as shown by reduced fractional shortening (%FS = 19.9%) and ejection fraction (%EF = 35.8%) relative to wild-type (%FS = 41.6%; %EF = 65.1%)

homeostasis/metabolism
• at E14.5, about 50% of homozygotes are edematous consistent with an early heart defect

respiratory system
• at E18.5, most homozygotes gasp for breath

nervous system
• at E9.5, homozygous mutant embryos exhibit an open cranial neural tube
• 9% of E14.5 and 4% of E18.5 homozygotes display exencephaly with a 'cauliflower-like' protrusion of the mutant brain

muscle
• at E14.5 and E18.5, homozygotes display hypertrophic trabeculae with deep intertrabecular recesses
• homozygotes display an apparently normal skeletal muscle development through embryogenesis; however, lipid bilayer experiments indicate that both skeletal (RyR1) and cardiac (RyR2) ryanodinereceptors show altered single-channel properties
• homozygotes exhibit severe dilated cardiomyopathy associated with aberrant single-channel gating properties of both skeletal and cardiac ryanodinereceptors
• a single 14-mo-old homozygote displayed reduced contractile activity in the ventricular wall, as shown by reduced fractional shortening (%FS = 19.9%) and ejection fraction (%EF = 35.8%) relative to wild-type (%FS = 41.6%; %EF = 65.1%)

liver/biliary system
• at E14.5, many homozygotes exhibit severe liver hemorrhage
• at E14.5, many homozygotes exhibit prominent liver necrosis

embryogenesis
• at E9.5, homozygous mutant embryos exhibit an open cranial neural tube

integument
• at E18.5, most homozygotes show pallor despite normal hematocrits

Mouse Models of Human Disease
OMIM IDRef(s)
Barth Syndrome; BTHS 302060 J:45536