Phenotypes associated with this allele

• Allele Symbol: Fkrp^tm1Scbr
• Allele Name: targeted mutation 1, S C Brown
• Allele ID: MGI:4835411
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fkrp^tm1Scbr/Fkrp^tm1Scbr	involves: C57BL/6	MGI:4835416
cn2	Fkrp^tm1Scbr/Fkrp^tm1Scbr Sox1^tm1(cre)Take/Sox1^+ Tg(CAG-LARGE)126Fmu/0	involves: C57BL/6NCrlj * C57BL/10 * CBA/Ca * CBA/JNCrlj	MGI:5556065
cn3	Fkrp^tm1Scbr/Fkrp^tm1Scbr Sox1^tm1(cre)Take/Sox1^+	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:5556062
ot4	Fkrp^tm1Scbr/?	Not Specified	MGI:6303809

Genotype
MGI:4835416

hm1

• Allelic Composition: Fkrp^tm1Scbr/Fkrp^tm1Scbr
• Genetic Background: involves: C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:164634 )

• mice die at or soon after birth

muscle

abnormal extensor digitorum longus morphology ( J:164634 )

• an increase in the percentage of fibers with central nuclei

abnormal tibialis anterior morphology ( J:164634 )

• an increase in the percentage of fibrers with central nuclei

centrally nucleated skeletal muscle fibers ( J:164634 )

• an increase in the percentage of fibers with central nuclei in the tibialis anterior and extensor digitorum longus

decreased skeletal muscle fiber number ( J:164634 )

• fore and hindlimb muscles show a reduction in fiber density

homeostasis/metabolism

edema ( J:164634 )

• muscle oedema

vision/eye

abnormal vitreous body morphology ( J:164634 )

• presence of ectopic nuclei, outside the inner limiting membrane (ILM), within the vitreous body of the mutant

nervous system

abnormal radial glial cell morphology ( J:164634 )

• the radial glia are disorganized and the radial glial endfeet fail to form the glial limitans at the pial surface thus resulting in a disruption of the glial scaffold

abnormal cerebral cortex morphology ( J:164634 )

• clear disruption of the neuronal layering of the cerebral cortex and partial fusion of the intrahemispheric fissue

• a marked alteration in the density and distribution of nuclei at different levels throughout the cortex, and a reduction in the total number of nuclei

growth/size/body

decreased body weight ( J:164634 )

• about one third the wild-type weight at birth

cellular

abnormal radial glial cell morphology ( J:164634 )

• the radial glia are disorganized and the radial glial endfeet fail to form the glial limitans at the pial surface thus resulting in a disruption of the glial scaffold

limbs/digits/tail

abnormal extensor digitorum longus morphology ( J:164634 )

• an increase in the percentage of fibers with central nuclei

abnormal tibialis anterior morphology ( J:164634 )

• an increase in the percentage of fibrers with central nuclei

Genotype
MGI:5556065

cn2

• Allelic Composition: Fkrp^tm1Scbr/Fkrp^tm1Scbr; Sox1^tm1(cre)Take/Sox1⁺; Tg(CAG-LARGE)126Fmu/0
• Genetic Background: involves: C57BL/6NCrlj * C57BL/10 * CBA/Ca * CBA/JNCrlj

mortality/aging

premature death ( J:207119 )

• poor health results in sacrifice at around 27 weeks of age

muscle

abnormal muscle morphology ( J:207119 )

• individual muscle fibers are occasionally surrounded by moderate to large amounts of compact, fibrous connective tissue and infiltrates of fat with some muscle fibers mineralized

centrally nucleated skeletal muscle fibers ( J:207119 )

skeletal muscle hypertrophy ( J:207119 )

• mice surviving to 30 weeks exhibit hypertrophy of muscle fibers

skeletal muscle fibrosis ( J:207119 )

calcified muscle ( J:207119 )

• presence of large calcium deposits in muscle

dystrophic muscle ( J:207119 )

• mice display more severe muscle phenotype than Fkrp^tm1Scbr Sox1^tm1(cre)Take mice

• variation in fiber size, centrally nucleated muscle fibers and increases in the number of split fibers at 12 weeks of age

• pronounced expansion of the interstitium with small to moderate amounts of variably mature fibroadipose tissue and substantial inflammation in the interstitium and necrotic muscle fibers comprised of neutrophils, macrophages, and lesser numbers of lymphocytes and plasma cells

abnormal muscle physiology ( J:207119 )

• muscle shows a reduction in resistance to eccentric contraction-induced injury (isometric force in the last contraction) relative to controls

myositis ( J:207119 )

• substantial inflammation in the interstitium and necrotic muscle fibers comprised of neutrophils, macrophages, and lesser numbers of lymphocytes and plasma cells

behavior/neurological

abnormal reflex ( J:207119 )

• partial collapse of the leg extensor reflex

immune system

myositis ( J:207119 )

• substantial inflammation in the interstitium and necrotic muscle fibers comprised of neutrophils, macrophages, and lesser numbers of lymphocytes and plasma cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2I		DOID:0110299	OMIM:607155	J:207119

Genotype
MGI:5556062

cn3

• Allelic Composition: Fkrp^tm1Scbr/Fkrp^tm1Scbr; Sox1^tm1(cre)Take/Sox1⁺
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

mortality/aging

postnatal lethality, incomplete penetrance ( J:207119 )

• fewer than the expected numbers are seen when double heterozygotes are mated to single heterozygous Fkrp mutant mice

• high pre-weaning loss is seen when double heterozygotes are mated together

growth/size/body

decreased body weight ( J:207119 )

♀ • females, but not males, show a reduced body weight at 20 but not at 12 weeks of age

muscle

myositis ( J:207119 )

• macrophages, lymphocytes, and rare plasma cells infiltrate the interstitium and necrotic myofibers

centrally nucleated skeletal muscle fibers ( J:207119 )

dystrophic muscle ( J:207119 )

• mice develop a progressive muscular dystrophy

• by 6 weeks of age, occasional areas of small basophilic regenerating fibers and inflammatory infiltrates are see in gastrocnemius muscle

• by 12 weeks of age, the gastrocnemius and diaphragm show fiber degeneration characterized by sarcoplasmic hyalinization, loss of cross striations and sarcoplasmic fragmentation and groups of small, regenerative myofibers with large, centralized nuclei and a granular pale basophilic cytoplasm

• at 30 weeks, muscle fiber degeneration is attenuated and regeneration with clusters of basophilic regenerative fibers is occasionally evident together with rare, interstitial lymphoplasmacytic foci

• however, the soleus muscle shows only minimal damage even at 30 weeks of age

muscle degeneration ( J:207119 )

• gastrocnemius and diaphragm muscles show onset of fiber degeneration at around 6 weeks of age

immune system

myositis ( J:207119 )

• macrophages, lymphocytes, and rare plasma cells infiltrate the interstitium and necrotic myofibers

nervous system

hydrocephaly ( J:207119 )

• when double heterozygotes are mated together, some homozygous Fkrp offspring exhibit hydrocephalus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2I		DOID:0110299	OMIM:607155	J:207119

Genotype
MGI:6303809

ot4

• Allelic Composition: Fkrp^tm1Scbr/?
• Genetic Background: Not Specified

nervous system

abnormal radial glial cell morphology ( J:258757 )

• disruption of the radial glial scaffold, with radial glial processes often haphazardly arranged and complete disruption of the glia limitans

abnormal cortical marginal zone morphology ( J:258757 )

• no marginal zone is seen

abnormal Cajal-Retzius cell morphology ( J:258757 )

• majority of Cajal-Retzius cells are located around the anterior cerebral artery and scattered Cajal-Retzius cells are seen within the disorganized cortical plate unlike in wild-type mice where they are present multifocally within the superficial molecular layer

• decrease in the number of Cajal-Retzius cells in the rostral cortex at the level of the corpus callosum and a concurrent increase in the number of Cajal-Retzius cells at the level of the hippocampus, suggesting a failure of tangential migration of these cells

abnormal cortical plate morphology ( J:258757 )

• the cortical plate is not apparent

abnormal cerebellum external granule cell layer morphology ( J:258757 )

• 2 of 5 mice exhibit subtle cerebellar lesions characterized by disruption of the external granule cell layer

hydrocephaly ( J:258757 )

• in 3 of 5 mice

dilated lateral ventricle ( J:258757 )

• 3 of 5 mice exhibit dilation of the lateral ventricles indicative of hydrocephalus

abnormal tectum morphology ( J:258757 )

• abnormalities in the tectum but to a lesser extent than in the cortex

abnormal inferior colliculus morphology ( J:258757 )

• the inferior and superior colliculi are disrupted, with substantial defects in the pia where large numbers of cells form a prominent subarachnoid layer

abnormal superior colliculus morphology ( J:258757 )

• the inferior and superior colliculi are disrupted, with substantial defects in the pia where large numbers of cells form a prominent subarachnoid layer

abnormal dentate gyrus morphology ( J:258757 )

• 2 of 5 mice show disrupted dentate gyrus of the hippocampus

abnormal neocortex morphology ( J:258757 )

• the rostral cortex is disrupted at P0

• rostral cortex shows a complete absence of laminar organization, with no obvious structure to the cortical plate, and fusion of the interhemispheric fissure

• at the hippocampus level, the lateral aspects of the cortex are extensively disrupted while the cortical plate is established and there is incomplete formation of the interhemispheric fissure with interdigitation of neurons from opposing cortical plates

• at the level of the corpus callosum, disorganization is more pronounced laterally

• mice exhibit a rostrocaudal gradient in the severity of brain lesions, with lesions most pronounced in the rostral cortex and progressively milder more caudally

abnormal cerebellar hemisphere morphology ( J:258757 )

• fusion of the cortical hemispheres with interdigitation of neurons from opposing cortical plates

abnormal meninges morphology ( J:258757 )

• leptomeningeal architecture is disrupted, with little distinction between the superficial arachnoid mater, the subarachnoid space, and the pia matter

abnormal brain pia mater morphology ( J:258757 )

• the pia is not apparent

ectopic neuron ( J:258757 )

• large numbers of heterotopic neurons and glial cells are present superficial to the glia limitans, expanding the subarachnoid space

cellular

abnormal radial glial cell morphology ( J:258757 )

• disruption of the radial glial scaffold, with radial glial processes often haphazardly arranged and complete disruption of the glia limitans

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
muscular dystrophy-dystroglycanopathy type B1		DOID:0050588	OMIM:613155	J:258757