Phenotypes associated with this allele

• Allele Symbol: Fktn^tm1Ttd
• Allele Name: targeted mutation 1, Tatsushi Toda
• Allele ID: MGI:3577652
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fktn^tm1Ttd/Fktn^tm1Ttd	involves: 129S7/SvEvBrd * C57BL/6	MGI:3577900
ht2	Fktn^tm1Ttd/Fktn^tm2(FCMD)Ttd	involves: 129S7/SvEvBrd	MGI:3832641
cx3	Dysf^im/Dysf^im Fktn^tm1Ttd/Fktn^tm2(FCMD)Ttd	involves: 129S7/SvEvBrd * C57BL/6 * SJL/J	MGI:5700212
cx4	Dysf^im/Dysf^+ Fktn^tm1Ttd/Fktn^tm2(FCMD)Ttd	involves: 129S7/SvEvBrd * C57BL/6 * SJL/J	MGI:5700213

Genotype
MGI:3577900

hm1

• Allelic Composition: Fktn^tm1Ttd/Fktn^tm1Ttd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:97950 )

• survival rate decreased gradually during the egg cylinder stage, with no survival beyond E9.5

embryonic lethality between implantation and placentation, incomplete penetrance ( J:97950 )

• survival rate decreased gradually during the egg cylinder stage, with no survival beyond E9.5

embryo

increased embryonic epiblast cell apoptosis ( J:97950 )

• increased number of apoptotic cells in E6.5 and E7.5 homozygous null embryos, predominantly in the epiblast region

abnormal developmental patterning ( J:97950 )

• at E6.5 and E7.5, some homozygous null embryos exhibited distorted and folded shapes

• border between epiblast and visceral endoderm is obscure in some E6.5 and E7.5 homozygous null embryos

embryonic growth arrest ( J:97950 )

• some homozygous null embryos arrest at E7.5

decreased embryo size ( J:97950 )

• some embryos were smaller than wildtype at E7.5 and E8.5, with larger extraembryonic portions than embryonic portions at E7.5

abnormal egg cylinder morphology ( J:97950 )

• the axis of the egg cylinder is distorted in some E6.5 embryos, so that the ectoplacental cone is attached to the apex

abnormal Reichert's membrane morphology ( J:97950 )

• Reichert's membrane appeared wavy

abnormal Reichert's membrane thickness ( J:97950 )

• Reichert's membrane exhibited variable thickness

absent Reichert's membrane ( J:97950 )

• concave face of the folded embryo lacked Reichert's membrane

abnormal visceral yolk sac cavity morphology ( J:97950 )

• maternal red blood cells were present in the yolk sac cavity of some E6.5 homozygous null embryos

growth/size/body

decreased embryo size ( J:97950 )

• some embryos were smaller than wildtype at E7.5 and E8.5, with larger extraembryonic portions than embryonic portions at E7.5

cellular

increased embryonic epiblast cell apoptosis ( J:97950 )

• increased number of apoptotic cells in E6.5 and E7.5 homozygous null embryos, predominantly in the epiblast region

impaired basement membrane formation ( J:97950 )

• basement membrane was thin, partly detached from the plasma membrane, and partly breached

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fukuyama congenital muscular dystrophy		DOID:0050559	OMIM:253800	J:97950

Genotype
MGI:3832641

ht2

• Allelic Composition: Fktn^tm1Ttd/Fktn^tm2(FCMD)Ttd
• Genetic Background: involves: 129S7/SvEvBrd

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:144746 )

• mice exhibit hypoglycosylation of alpha-dystroglycan compared to in wild-type mice

• however, glycosylation of alpha-dystrophan can be restored by ectopic expression of LARGE

• laminin-binding activity of alpha-dystroglycan is 50% of normal

nervous system

abnormal neuronal migration ( J:144746 )

• a few mice exhibit a very small ectopic cluster of neurons migrating into the marginal zone are observed unlike in wild-type mice

• however, brain morphology is otherwise normal

muscle

muscle phenotype ( J:144746 )

N • despite alpha-dystroglycan hypoglycosylation, no evidence of muscular dystrophy is observed at birth or in older mice

N • even after exercise exhaustion, muscle cell membrane permeability is normal

cellular

abnormal neuronal migration ( J:144746 )

• a few mice exhibit a very small ectopic cluster of neurons migrating into the marginal zone are observed unlike in wild-type mice

• however, brain morphology is otherwise normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fukuyama congenital muscular dystrophy		DOID:0050559	OMIM:253800	J:144746
muscular dystrophy-dystroglycanopathy type B1		DOID:0050588	OMIM:613155	J:144746

Genotype
MGI:5700212

cx3

• Allelic Composition: Dysf^im/Dysf^im; Fktn^tm1Ttd/Fktn^tm2(FCMD)Ttd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL/J

muscle

myositis ( J:221523 )

• macrophage infiltration is increased in skeletal muscle compared to mice homozygous for Dysf^im and heterozygous for Fktn^tm2(FCMD)Ttd

abnormal skeletal muscle morphology ( J:221523 )

• increases of connective tissue infiltrations in skeletal muscles

abnormal skeletal muscle fiber morphology ( J:221523 )

• albumin-positive myofibers are increased in skeletal muscle indicating deterioration of the myofiber membrane fragility

centrally nucleated skeletal muscle fibers ( J:221523 )

• at 15 weeks and 30 weeks of age, but not at 8 weeks, mutants show significantly more fibers with centrally located nuclei than do mice homozygous for Dysf^im and heterozygous for Fktn^tm2(FCMD)Ttd, indicating more frequent cycles of muscle cell degeneration and regeneration

• the proportion of fibers with centrally located nuclei increases with age

skeletal muscle fiber degeneration ( J:221523 )

• at 15 and 30 weeks of age, but not at 8 weeks, mutants show more frequent cycles of muscle cell degeneration and regeneration

skeletal muscle fibrosis ( J:221523 )

• fibrotic area is increased in skeletal muscle

dystrophic muscle ( J:221523 )

• mice show further progressed and more severe dystrophic features than mice homozygous for Dysf^im and heterozygous for Fktn^tm2(FCMD)Ttd in quadriceps, gastrocnemius, and tibialis anterior muscles

immune system

myositis ( J:221523 )

• macrophage infiltration is increased in skeletal muscle compared to mice homozygous for Dysf^im and heterozygous for Fktn^tm2(FCMD)Ttd

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fukuyama congenital muscular dystrophy		DOID:0050559	OMIM:253800	J:221523

Genotype
MGI:5700213

cx4

• Allelic Composition: Dysf^im/Dysf⁺; Fktn^tm1Ttd/Fktn^tm2(FCMD)Ttd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL/J

muscle

muscle phenotype ( J:221523 )

N • mice do not show any obvious features of muscular dystrophy