growth/size/body region phenotype

• decreased body weight
  • homozygotes display a slight reduction in body mass
  (MGI Ref ID J:67176)

immune system phenotype

• increased susceptibility to endotoxin shock
  • within 3 hours of challenge by LPS, homozygotes display decreased induction of the adhesion molecules E-selectin, P-selectin and VCAM1, as well as the cytokines tumor necrosis factor, interleukin 1 beta (IL1B) and IL-6, and CXCL1 compared with wild-type
  (MGI Ref ID J:67176)
  • homozygotes display increased susceptibility to death from LPS plus D-galactosamine injection
  (MGI Ref ID J:67176)

• increased susceptibility to Picornaviridae infection
  • homozygotes are more susceptible to Coxsackievirus B3 infection than wild-type control mice
  (MGI Ref ID J:67176)

• increased susceptibility to viral infection
  • compared with wild-type, homozygotes are more susceptible to Coxsackievirus B3 infection, and exhibit a higher incidence of mononuclear pulmonary infiltrates following exposure to Herpes simplex virus-1
  (MGI Ref ID J:67176)

• increased susceptibility to Herpesvirales infection
  • following exposure to Herpes simplex virus-1, homozygotes exhibit a higher incidence of mononuclear pulmonary infiltrates than wild-type control mice
  (MGI Ref ID J:67176)

• abnormal cytokine secretion
  • Normal - notably, T lymphocytes from anti-CD3-treated mutant mice produce normal levels of IL-2 at 24 hours and of IFN-gamma, IL-4, and IL-6 at 48 hours
  (MGI Ref ID J:67176)
  • three hours after T cell activation via i.v. injection with anti-CD3 antibody, mutant spleens display less induction of IL-2, IL-4 and IL-6 mRNA compared with wild-type spleens
  (MGI Ref ID J:67176)

mammalian phenotype

• immune system phenotype
  • Normal - homozygotes show normal counts of circulating granulocytes and normal lymphocyte cell numbers in lymph nodes, spleen and thymus
  (MGI Ref ID J:67176)

hearing/vestibular/ear phenotype

• abnormal utricular macula morphology
  • the macula of utricle is atrophic, with significant reductions in numbers of sensory cells, stereocilia and otoconia
  (MGI Ref ID J:30611)

• decreased vestibular hair cell stereocilia number
  • significant reductions in numbers of vestibular hair cell stereocilia
  (MGI Ref ID J:30611)

• impaired hearing
  • homozygotes display decreased hearing
  (MGI Ref ID J:30611)

• abnormal vestibular saccular macula morphology
  • the macula of the saccule is atrophic, with significant reductions in numbers of sensory cells, stereocilia and otoconia
  (MGI Ref ID J:30611)

• decreased otolith number
  • significant reductions in numbers of otoconia
  (MGI Ref ID J:30611)

• decreased vestibular hair cell number
  • significant reductions in numbers of vestibular sensory cells
  (MGI Ref ID J:30611)

immune system phenotype

• increased susceptibility to bacterial infection
  • higher doses of LPS lead to equal induction of E-selectin mRNA in both genotypes
  (MGI Ref ID J:30611)
  • in contrast to wild-type, homozygotes display poor induction of E-selectin three hours after intraperitoneal injection of LPS at doses up to 50 microg
  (MGI Ref ID J:30611)

• eye inflammation
  • 50% of homozygotes spontaneously develop periocular neutrophilic/lymphocytic infiltrates
  (MGI Ref ID J:30611)

limbs/digits/tail phenotype

• short limbs
  • the limb length decrease is rhizomelic, with more severe shortening in proximal bony segments than distal ones
  (MGI Ref ID J:30611)

mortality/aging

• postnatal lethality, incomplete penetrance
  • Normal - the lifespan of surviving homozygotes is, however, normal
  (MGI Ref ID J:30611)
  • two waves of deaths occur: one within the initial 2 days of life and one near weaning
  (MGI Ref ID J:30611)
  • only 51% of homozygous null mice survive past 1 month
  (MGI Ref ID J:30611)

nervous system phenotype

• enlarged brain ventricles
  • brains of homozygous null mice display enlarged ventricles
  (MGI Ref ID J:30611)

• decreased brain size
  (MGI Ref ID J:30611)

• decreased vestibular hair cell number
  • significant reductions in numbers of vestibular sensory cells
  (MGI Ref ID J:30611)

• abnormal vestibular ganglion morphology
  • vestibular ganglia have decreased neuron cell bodies
  (MGI Ref ID J:30611)

• decreased Purkinje cell number
  • homozygotes display a 50% decrease in Purkinje cells at the cerebellar molecular-granular cell layer boundary
  (MGI Ref ID J:30611)

• ectopic Purkinje cell
  • numerous large Purkinje-like cells are distributed throughtout the otherwise normal-appearing granular cell layer of the cerebellum
  (MGI Ref ID J:30611)

• decreased vestibular hair cell stereocilia number
  • significant reductions in numbers of vestibular hair cell stereocilia
  (MGI Ref ID J:30611)

behavior/neurological phenotype

• head tossing
  • homozygotes exhibit vertical head tossing
  (MGI Ref ID J:30611)

• head shaking
  • homozygotes display abnormal twitches of the head
  (MGI Ref ID J:30611)

• hyperactivity
  (MGI Ref ID J:30611)

• impaired limb coordination
  • homozygotes exhibit decreased hind limb coordination
  (MGI Ref ID J:30611)

• tremors
  • homozygotes show a characteristic fine-amplitude whole-body tremor
  (MGI Ref ID J:30611)

• ataxia
  (MGI Ref ID J:30611)

skeleton phenotype

• disorganized long bone epiphyseal plate
  • bones show disorganization in the sequence of endochondral ossification at epiphyseal growth plates
  (MGI Ref ID J:30611)

• abnormal long bone epiphyseal plate morphology
  • in vivo labelling of cartilage cells with 3H-thymidine confirmed that growth-plate cartilage cell division is significantly reduced
  (MGI Ref ID J:30611)

• chondrodystrophy
  • the dysmorphology of epiphyseal plates coupled with the variable penetrance of the bone abnormality is reminiscent of human hypochondroplasia
  (MGI Ref ID J:30611)

• abnormal chondrocyte morphology
  • homozygotes exhibit abnormal clusters of cells instead of ordered columns of chondrocytes, seams of bone covering the metaphyseal side of the physes, and lack of ingrowth of chondroclasts and capillaries
  (MGI Ref ID J:30611)

• decreased long bone epiphyseal plate size
  • homozygotes lack normal-appearing cartilaginous trabeculae extending from the physes and have distinctly thin epiphyseal growth plates
  (MGI Ref ID J:30611)

vision/eye phenotype

• eye inflammation
  • 50% of homozygotes spontaneously develop periocular neutrophilic/lymphocytic infiltrates
  (MGI Ref ID J:30611)

growth/size/body region phenotype

• proportional dwarf
  • surviving homozygotes are mildly to severely runted
  (MGI Ref ID J:30611)
  • dwarfism is uniform, with the reduced spine length proportional to the shortened extremities
  (MGI Ref ID J:30611)

• decreased body weight
  • surviving homozygotes reach approximately 71% of the weight of sex-matched wild-type littermates
  (MGI Ref ID J:30611)

mortality/aging

• postnatal lethality
  • heterozygous mice are phenotypically normal but display an increased postnatal mortality rate that is roughly half that of homozygotes, consistent with a gene dosage effect
  (MGI Ref ID J:30611)