Mouse Genome Informatics
hm1
    Fig4plt1/Fig4plt1
B6.Cg-Fig4plt1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Presence of vacuoles in the atria of E18.5 Fig4plt1/Fig4plt1 mutants

cardiovascular system
• significant degeneration of the atria with large, transparent vacuoles


Mouse Genome Informatics
hm2
    Fig4plt1/Fig4plt1
involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survive to 1 -2 months of age

nervous system
• extensive autophagic inclusion bodies
• thinning of the myelin sheath of the sciatic nerve
• thinning of the myelin sheath of the sciatic nerve
• in the sciatic nerve
• severe spongiform degeneration in the brain and extensive loss of neurons from the peripheral ganglia
• extensive loss of neurons from peripheral ganglia
• neurons in layers 4 and 5 of the cortex, the deep cerebellar nuclei, and the dorsal root ganglia are severely affected with accumulation of vacuoles that fill the cytoplasm

pigmentation

integument


Mouse Genome Informatics
hm3
    Fig4plt1/Fig4plt1
involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die by 6 weeks (J:122737)
• juvenile lethality at 6-8 weeks of age (J:185989)

behavior/neurological
• severe movement disorder by 30 days of age
• by 30 days of age (J:185989)
• progressive loss of mobility
• at week 3
• mice have a 'swimming' gait

nervous system
• at 6 weeks, spinal motor neurons accumulates vacuoles prior to cell loss
• visible at week 1, mice exhibit neonatal degeneration in sensory and autonomic ganglia with loss of neurons in from layers 4 and 5 of the cortex, deep cerebellar nuclei, thalamus, pons and medulla
• mice exhibit fewer large-diameter myelinated axons
• sciatic nerve conduction velocity is slowed
• sciatic nerves have reduced amplitude of compound muscle action potential
• reduced sciatic nerve myelination
• low abundance of myelin basic protein
• sciatic nerves have reduced amplitude of compound muscle action potential
• sciatic nerve conduction velocity is slowed (J:122737)
• sciatic nerve conduction velocity reduced to 50% of velocity in control mice (J:185989)
• in deep layers of cortex, cerebellar nuclei, hippocampus, brainstem, and dorsal root ganglia

muscle

growth/size

hematopoietic system
• severe tremors develop 2 weeks after birth

immune system
• severe tremors develop 2 weeks after birth

pigmentation
• at P3 (J:122737)
• clumps of melanosomes are visible in the few remaining pigmented hair follicles

integument
• at P3 (J:122737)
• clumps of melanosomes are visible in the few remaining pigmented hair follicles
• pigment containing hair follicles are decreased in number

Mouse Models of Human Disease
OMIM IDRef(s)
Charcot-Marie-Tooth Disease, Type 4j; CMT4J 611228 J:122737


Mouse Genome Informatics
hm4
    Fig4plt1/Fig4plt1
involves: 129P2/OlaHsd * C3H * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• impaired growth; skeleton is normal at birth but is smaller at P21

craniofacial
• craniofacial morphology is altered
• relative overgrowth of incisors

hematopoietic system
• extensive vacuolization is seen in cultures of bone marrow mesenchymal stroma

skeleton
• skeleton is normal at birth but is smaller at P21
• clavicles are 20-25% smaller at P21 than in wild-type, however their shape is normal
• however, pelvic bone shape is normal in newborns and at P21
• long bones are 20-25% smaller at P21 than in wild-type
• bone volume fraction, bone surface, trabecular number and connectivity density are reduced to less than 50% of wild-type values
• lower cortical density of bones
• femoral cortical thickness is reduced to less than 50% of wild-type values
• extensive vacuolization is seen in cultures of isolated osteoblasts from calvarial tissue
• lower trabecular density of bones and reduction in size and density of trabeculae in vertebrae
• trabecular separation is increased more than 3-fold

limbs/digits/tail
N
• mice do not exhibit aplasia or hypoplasia of digits on the front or rear limb (J:203638)

Mouse Models of Human Disease
OMIM IDRef(s)
Yunis-Varon Syndrome; YVS 216340 J:203638


Mouse Genome Informatics
cx5
    Fig4plt1/Fig4plt1
Tg(ACTB-Fig4*I41T)705Mm/0

involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival is increased to 3?6 months compared to from 1?2 months in Fig4 null mice not carrying the transgene

nervous system
N
• unlike in null mice not carrying the transgene, myelin sheath thinning is not seen (J:173446)
• intermediate level of autophagic inclusion bodies
• high pressure hydrocephalus is indicated by the compression of the cerebellum and hippocampus
• intermediate level compared to null mice not carrying the transgene
• reduced at 4 and 14 months of age in the sciatic nerve but not as much as in null mice not carrying the transgene
• intermediate level of degeneration compared to null mice not carrying the transgene
• degeneration of the cerebellar nuclei

craniofacial

integument

pigmentation

skeleton

Mouse Models of Human Disease
OMIM IDRef(s)
Charcot-Marie-Tooth Disease, Type 4j; CMT4J 611228 J:173446


Mouse Genome Informatics
cx6
    Fig4plt1/Fig4plt1
Tg(ACTB-Fig4*I41T)721Mm/0

involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• survival is completely corrected compared to Fig4 null mice not carrying the transgene (J:173446)

nervous system
N
• unlike in null mice not carrying the transgene, myelin sheath thinning is not seen (J:173446)
• a few autophagic inclusion bodies are present
• astrocytosis is almost completely corrected compared to null mice not carrying the transgene
• reduced at 4 and 14 months of age in the sciatic nerve but not as much as in null mice not carrying the transgene
• unlike in null mice not carrying the transgene, dorsal root ganglia are intact at P90
• degeneration of the cerebellar nuclei
• minimal spongiform degeneration unlike in null mice not carrying the transgene

pigmentation
• partial rescue of reduced pigmentation compared to null mice not carrying the transgene


Mouse Genome Informatics
cx7
    Fig4plt1/Fig4plt1
Tg(Eno2-Fig4)#Mm/?

involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 65% of mice live 10 months or more

growth/size
• growth rate is improved during the first month relative to Fig4plt1 homozygotes

nervous system
N
• spongiform degeneration corrected at 3 weeks of age and in mice 9 and 12 months old (J:185989)
• dorsal root ganglion spongiform degeneration also improved (J:185989)
• sciatic nerve conduction velocity normal (J:185989)
• normal sciatic nerve myelination (J:185989)


Mouse Genome Informatics
cx8
    Fig4plt1/Fig4plt1
Tg(GFAP-Fig4)#Mm/?

involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival not corrected relative to Fig4plt1 homozygotes

growth/size
• growth not corrected relative to Fig4plt1 homozygotes

behavior/neurological
• severe movement disorder by 30 days of age
• by 30 days of age

nervous system
N
• astrogliosis mostly corrected (J:185989)
• reduced sciatic nerve myelination
• low abundance of myelin basic protein