Phenotypes associated with this allele

• Allele Symbol: Fktn^tm2(FCMD)Ttd
• Allele Name: targeted mutation 2, Tatsushi Toda
• Allele ID: MGI:3690337
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fktn^tm2(FCMD)Ttd/Fktn^tm2(FCMD)Ttd	Not Specified	MGI:3696430
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
cx5	Dysf^im/Dysf^im Fktn^tm2(FCMD)Ttd/Fktn^+	involves: C57BL/6 * SJL/J	MGI:5700214

Genotype
MGI:3696430

hm1

• Allelic Composition: Fktn^tm2(FCMD)Ttd/Fktn^tm2(FCMD)Ttd
• Genetic Background: Not Specified

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

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:114512 , J:144746 )

• 0-mannose beta1, 2-N-acetylglucosaminyltransferase 1 (POM-GnT1) enzymatic activity is reduced by about 30%, resulting in hypoglycosylated alpha-dystroglycan (J:114512)

• mice exhibit hypoglycosylation of alpha-dystroglycan compared to in wild-type mice (J:144746)

muscle

muscle phenotype ( J:144746 )

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

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

Genotype
MGI:5700214

cx5

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

muscle

abnormal skeletal muscle fiber morphology ( J:221523 )

• albumin-positive myofibers are only sparsely seen in skeletal muscles indicating latent membrane fragility

centrally nucleated skeletal muscle fibers ( J:221523 )

skeletal muscle fiber necrosis ( J:221523 )

dystrophic muscle ( J:221523 )

• mice show mild dystrophic changes such as the presence of necrotic fibers and centrally located nuclei