Phenotypes associated with this allele

• Allele Symbol: Hsf1^tm1Ijb
• Allele Name: targeted mutation 1, Ivor J Benjamin
• Allele ID: MGI:2155444
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hsf1^tm1Ijb/Hsf1^tm1Ijb	129.129S6-Hsf1^tm1Ijb	MGI:3606147
hm2	Hsf1^tm1Ijb/Hsf1^tm1Ijb	either: (involves: 129S6/SvEvTac * 129X1/SvJ) or (involves: 129S6/SvEvTac * BALB/c) or (involves: 129S6/SvEvTac * C57BL/6J) or (involves: 129S6/SvEvTac * ICR)	MGI:3606146
hm3	Hsf1^tm1Ijb/Hsf1^tm1Ijb	involves: 129S6/SvEvTac	MGI:5285095
cx4	Hsf1^tm1Ijb/Hsf1^tm1Ijb Tg(TTR-V30M)15Imeg/0	involves: 129S6/SvEvTac * BALB/c * C57BL/6	MGI:4429562

Genotype
MGI:3606147

hm1

• Allelic Composition: Hsf1^tm1Ijb/Hsf1^tm1Ijb
• Genetic Background: 129.129S6-Hsf1^tm1Ijb

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

nervous system

abnormal astrocyte morphology ( J:93600 )

• longer processes

abnormal brain morphology ( J:93600 )

abnormal brain ventricle morphology ( J:93600 )

dilated lateral ventricle ( J:93600 )

dilated third ventricle ( J:93600 )

• slightly

abnormal brain white matter morphology ( J:93600 )

• reduced white matter

abnormal corpus callosum morphology ( J:93600 )

• spongiosis

abnormal striatum morphology ( J:93600 )

• spongiosis in the caudate putamen and external capsule

abnormal putamen morphology ( J:93600 )

• neurodegeneration in the caudate putamen

cellular

abnormal astrocyte morphology ( J:93600 )

• longer processes

Genotype
MGI:3606146

hm2

• Allelic Composition: Hsf1^tm1Ijb/Hsf1^tm1Ijb
• Genetic Background: either: (involves: 129S6/SvEvTac * 129X1/SvJ) or (involves: 129S6/SvEvTac * BALB/c) or (involves: 129S6/SvEvTac * C57BL/6J) or (involves: 129S6/SvEvTac * ICR)

mortality/aging

prenatal lethality, incomplete penetrance ( J:58383 , J:73593 )

• 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/body

decreased body weight ( J:58383 )

• significantly lower body weights observed in the first post natal week

postnatal growth retardation ( J:58383 )

• growth consistently lagged past weaning

• at 8 weeks of age, male weights 77% normal and female weights 78% normal

embryo

failure of zygotic cell division ( J:65267 )

• 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

abnormal extraembryonic tissue morphology ( J:58383 )

decreased spongiotrophoblast size ( J:58383 )

• thinning of spongiotrophoblast at E11.5 and becoming more pronounced at E13.5

abnormal placenta labyrinth morphology ( J:58383 )

• reduced size, fibrin deposits, vacuolization, degeneration and hemorrhages

reproductive system

female infertility ( J:58383 , J:65267 )

♀ • females infertile but males with normal fertility (J:58383)

♀ • zygotes fail to develop in homozygous mothers regardless of genotype (J:65267)

immune system

increased tumor necrosis factor secretion ( J:58383 )

• production increases 2X in response to lipopolysaccharide

increased susceptibility to bacterial infection ( J:58383 )

• significantly reduced survival when challenged with lipopolysaccharide

Genotype
MGI:5285095

hm3

• Allelic Composition: Hsf1^tm1Ijb/Hsf1^tm1Ijb
• Genetic Background: involves: 129S6/SvEvTac

reproductive system

abnormal chromosomal synapsis ( J:175085 )

• 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

abnormal female meiosis ( J:175085 )

♀ • at P1 only 51% of oocytes have reached the diplotene stage compared to 80% of oocytes in heterozygous controls

♀ • in pachytene oocytes the number of MSH4 foci is significantly reduced and the DNA repair process is abnormal

♀ • in oocytes chromosomal length is significantly increased at metaphase I

♀ • significantly blocked in the pro-Mi/MI phase

abnormal meiotic spindle assembly checkpoint ( J:175085 )

• persistent activation of the spindle assembly checkpoint in oocytes

abnormal synaptonemal complex ( J:175085 )

• in oocytes the length of the synaptonemal complex (SC) is significantly increased

cellular

abnormal chromosomal synapsis ( J:175085 )

• 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

abnormal female meiosis ( J:175085 )

♀ • at P1 only 51% of oocytes have reached the diplotene stage compared to 80% of oocytes in heterozygous controls

♀ • in pachytene oocytes the number of MSH4 foci is significantly reduced and the DNA repair process is abnormal

♀ • in oocytes chromosomal length is significantly increased at metaphase I

♀ • significantly blocked in the pro-Mi/MI phase

abnormal meiotic spindle assembly checkpoint ( J:175085 )

• persistent activation of the spindle assembly checkpoint in oocytes

abnormal synaptonemal complex ( J:175085 )

• in oocytes the length of the synaptonemal complex (SC) is significantly increased

Genotype
MGI:4429562

cx4

• Allelic Composition: Hsf1^tm1Ijb/Hsf1^tm1Ijb; Tg(TTR-V30M)15Imeg/0
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL/6

nervous system

nervous system phenotype ( J:156658 )

N • as in human patients with familial amyloidotic polyneuropathy, no transthyretin deposition is observed in the brain and spinal cord

abnormal axon morphology ( 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

abnormal dorsal root ganglion morphology ( J:156658 )

• 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

abnormal sciatic nerve morphology ( J:156658 )

• mice exhibit transthyretin depositions in the sciatic nerve unlike wild-type or Tg(TTR-V30M)15Imeg mice

neurodegeneration ( J:156658 )

• at 24 months, mice exhibit collagen pockets indicating neurodegeneration unlike in Tg(TTR-V30M)15Imeg mice

digestive/alimentary system

abnormal digestive system morphology ( J:156658 )

• 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

abnormal stomach morphology ( J:156658 )

• 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

increased interleukin-1 beta secretion ( J:156658 )

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

increased tumor necrosis factor secretion ( J:156658 )

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

integument

abnormal skin morphology ( J:156658 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
transthyretin amyloidosis		DOID:0050638	OMIM:105210	J:156658