Phenotypes Associated with This Genotype

Genotype
MGI:2655609

• Allelic Composition: Atf2^tm1Glm/Atf2^tm1Glm
• Genetic Background: involves: 129S2/SvPas

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:30611 )

• only 51% of homozygous null mice survive past 1 month

• two waves of deaths occur: one within the initial 2 days of life and one near weaning

• the lifespan of surviving homozygotes is, however, normal

behavior/neurological

tremors ( J:30611 )

• homozygotes show a characteristic fine-amplitude whole-body tremor

ataxia ( J:30611 )

impaired limb coordination ( J:30611 )

• homozygotes exhibit decreased hind limb coordination

head shaking ( J:30611 )

• homozygotes display abnormal twitches of the head

head tossing ( J:30611 )

• homozygotes exhibit vertical head tossing

hyperactivity ( J:30611 )

growth/size/body

decreased body weight ( J:30611 )

• surviving homozygotes reach approximately 71% of the weight of sex-matched wild-type littermates

proportional dwarf ( J:30611 )

• surviving homozygotes are mildly to severely runted

• dwarfism is uniform, with the reduced spine length proportional to the shortened extremities

hearing/vestibular/ear

decreased vestibular hair cell number ( J:30611 )

• significant reductions in numbers of vestibular sensory cells

decreased vestibular hair cell stereocilia number ( J:30611 )

• significant reductions in numbers of vestibular hair cell stereocilia

abnormal utricular macula morphology ( J:30611 )

• the macula of utricle is atrophic, with significant reductions in numbers of sensory cells, stereocilia and otoconia

abnormal vestibular saccular macula morphology ( J:30611 )

• the macula of the saccule is atrophic, with significant reductions in numbers of sensory cells, stereocilia and otoconia

decreased otolith number ( J:30611 )

• significant reductions in numbers of otoconia

impaired hearing ( J:30611 )

• homozygotes display decreased hearing

immune system

eye inflammation ( J:30611 )

• 50% of homozygotes spontaneously develop periocular neutrophilic/lymphocytic infiltrates

increased susceptibility to bacterial infection ( 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

• higher doses of LPS lead to equal induction of E-selectin mRNA in both genotypes

limbs/digits/tail

rhizomelic limb ( J:30611 )

• the limb length decrease is rhizomelic, with more severe shortening in proximal bony segments than distal ones

skeleton

abnormal long bone epiphyseal plate morphology ( J:30611 )

• in vivo labelling of cartilage cells with 3H-thymidine confirmed that growth-plate cartilage cell division is significantly reduced

decreased long bone epiphyseal plate size ( J:30611 )

• homozygotes lack normal-appearing cartilaginous trabeculae extending from the physes and have distinctly thin epiphyseal growth plates

disorganized long bone epiphyseal plate ( J:30611 )

• bones show disorganization in the sequence of endochondral ossification at epiphyseal growth plates

abnormal chondrocyte morphology ( J:30611 )

• 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

chondrodystrophy ( J:30611 )

• the dysmorphology of epiphyseal plates coupled with the variable penetrance of the bone abnormality is reminiscent of human hypochondroplasia

nervous system

decreased vestibular hair cell number ( J:30611 )

• significant reductions in numbers of vestibular sensory cells

decreased vestibular hair cell stereocilia number ( J:30611 )

• significant reductions in numbers of vestibular hair cell stereocilia

decreased brain size ( J:30611 )

enlarged brain ventricles ( J:30611 )

• brains of homozygous null mice display enlarged ventricles

decreased Purkinje cell number ( J:30611 )

• homozygotes display a 50% decrease in Purkinje cells at the cerebellar molecular-granular cell layer boundary

ectopic Purkinje cell ( J:30611 )

• numerous large Purkinje-like cells are distributed throughtout the otherwise normal-appearing granular cell layer of the cerebellum

abnormal vestibular ganglion morphology ( J:30611 )

• vestibular ganglia have decreased neuron cell bodies

vision/eye

eye inflammation ( J:30611 )

• 50% of homozygotes spontaneously develop periocular neutrophilic/lymphocytic infiltrates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteochondrodysplasia		DOID:2256		J:30611