Mouse Genome Informatics
hm1
    Hsf1tm1Ijb/Hsf1tm1Ijb
129.129S6-Hsf1tm1Ijb
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• reduced white matter
• spongiosis in the caudate putamen and external capsule
• neurodegeneration in the caudate putamen
• longer processes


Mouse Genome Informatics
hm2
    Hsf1tm1Ijb/Hsf1tm1Ijb
either: (involves: 129S6/SvEvTac * 129X1/SvJ) or (involves: 129S6/SvEvTac * BALB/c) or (involves: 129S6/SvEvTac * C57BL/6J) or (involves: 129S6/SvEvTac * ICR)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: lethality worse on a 129 background than on BALB/c, C57BL/6, or IRC backgrounds (J:58383)
• death starts to occur around E14 (J:58383)
• fewer homozygotes born than expected (J:73593)

growth/size
• significantly lower body weights observed in the first post natal week
• growth consistently lagged past weaning
• at 8 weeks of age, male weights 77% normal and female weights 78% normal

embryogenesis
• thinning of spongiotrophoblast at E11.5 and becoming more pronounced at E13.5
• reduced size, fibrin deposits, vacuolization, degeneration and hemorrhages
• zygotes from homozygous mothers fail to develop even when transplanted to wild-type mothers
• block at 1 cell stage, few ever reach 2 cell stage

reproductive system
• females infertile but males with normal fertility (J:58383)
• zygotes fail to develop in homozygous mothers regardless of genotype (J:65267)

immune system
• production increases 2X in response to lipopolysaccharide
• significantly reduced survival when challenged with lipopolysaccharide


Mouse Genome Informatics
hm3
    Hsf1tm1Ijb/Hsf1tm1Ijb
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• the percentage of univalent chromosomes is increased, single chromatids are present, and an increase in the percentage of separated centromeres suggesting impaired cohesion in oocytes at metaphase I
• at P1 only 51% of oocytes have reached the diplotene stage compared to 80% of oocytes in heterozygous controls (J:175085)
• in pachytene oocytes the number of MSH4 foci is significantly reduced and the DNA repair process is abnormal (J:175085)
• in oocytes chromosomal length is significantly increased at metaphase I (J:175085)
• significantly blocked in the pro-Mi/MI phase (J:175085)
• persistent activation of the spindle assembly checkpoint in oocytes
• in oocytes the length of the synaptonemal complex (SC) is significantly increased


Mouse Genome Informatics
cx4
    Hsf1tm1Ijb/Hsf1tm1Ijb
Tg(TTR-V30M)15Imeg/0

involves: 129S6/SvEvTac * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• as in human patients with familial amyloidotic polyneuropathy, no transthyretin deposition is observed in the brain and spinal cord (J:156658)
• after 24 months, mice exhibit a decrease in the number of unmyelinated fibers and myelinated fibers in sciatic nerves with transthyretin depositions unlike in wild-type mice
• at 3 months, some mice exhibit transthyretin depositions in the dorsal root ganglion unlike wild-type or Tg(TTR-V30M)15Imeg mice
• penetrance of thranthyretin increases with age
• mice exhibit transthyretin depositions in the sciatic nerve unlike wild-type or Tg(TTR-V30M)15Imeg mice
• at 24 months, mice exhibit collagen pockets indicating neurodegeneration unlike in Tg(TTR-V30M)15Imeg mice

digestive/alimentary system
• from 1 to 24 months of age, mice exhibit transthyretin depositions in the gastrointestinal tract unlike in wild-type mice
• mice exhibit a 2- to 3-fold higher penetrance of transthyretin deposition compared with Tg(TTR-V30M)15Imeg mice
• at 6 months, mice exhibit amyloid depositions in the stomach unlike wild-type mice
• a higher number of older mice exhibit amyloid depositions in the stomach

immune system
• in sciatic nerves and neurons of ganglion that exhibit transthyretin deposition
• in sciatic nerves and neurons of ganglion that exhibit transthyretin deposition

integument
• at 3 months, mice exhibit transthyretin depositions in the skin unlike wild-type or Tg(TTR-V30M)15Imeg mice

Mouse Models of Human Disease
OMIM IDRef(s)
Amyloidosis, Hereditary, Transthyretin-Related 105210 J:156658