Phenotypes Associated with This Genotype

Genotype
MGI:6721005

• Allelic Composition: Wdr45^em1Wrst/Wdr45^em1Wrst
• Genetic Background: involves: C57BL/6N * FVB

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:307284 )

♀N • female mice exhibit normal serum protein (total protein, albumin, and total iron binding capacity) levels

increased circulating glucose level ( J:307284 )

♀ • at 14 months of age

decreased circulating lactate level ( J:307284 )

♀

increased circulating iron level ( J:307284 )

♀ • slight with increased transferrin saturation

♀ • however, iron levels are normal in the brain and erythropoiesis organ

increased circulating aspartate transaminase level ( J:307284 )

♀ • at 14 months of age

increased circulating lactate dehydrogenase level ( J:307284 )

♀ • at 14 months of age

impaired glucose tolerance ( J:307284 )

♀ • mild delay in glucose clearance in female, but not male mice

increased alkaline phosphatase activity ( J:307284 )

♀ • at 14 months of age

nervous system

abnormal cerebellar Purkinje cell layer ( J:307284 )

♀ • impaired in the cerebellar cortex

astrocytosis ( J:307284 )

♀ • in the medulla oblongata

decreased dopaminergic neuron number ( J:307284 )

♀ • reduced dopamine positive neuroaxonal fibres in the substantia nigra

neurodegeneration ( J:307284 )

♀ • progressive with eosinophil spheroids and swollen structures in the basal ganglia, thalamus, cerebral cortex, medulla oblongata, spinal cord, and deep cerebellar nuclei

vision/eye

decreased cornea thickness ( J:307284 )

♀

increased eye anterior chamber depth ( J:307284 )

♀

decreased total retina thickness ( J:307284 )

♀ • in female, but not male, mice

retina degeneration ( J:307284 )

♀ • in some mice

behavior/neurological

limb grasping ( J:307284 )

♀

tremors ( J:307284 )

♀ • at 20 months

impaired coordination ( J:307284 )

♀ • increased falls on a balance beam and longer time to traverse a beam ladder with increased hindpaw slips

♀ • however, forepaw slips rate is normal

increased locomotor activity ( J:307284 )

♀ • increased distance traveled

growth/size/body

increased body weight ( J:307284 )

♀

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:307284 )

♀

impaired hearing ( J:307284 )

♀ • progressive starting at 17 months in a click-box test

hematopoietic system

hematopoietic system phenotype ( J:307284 )

♀ • female mice exhibit normal leukocyte and erythrocyte counts along with normal hemoglobin levels and hematocrit levels

anisocytosis ( J:307284 )

♀ • MP:0002642

pigmentation

lipofuscinosis ( J:307284 )

♀ • in the retina

♀ • however, no lipofuscin accumulation in the brain

cellular

abnormal mitochondrial ATP synthesis coupled electron transport ( J:307284 )

♀ • reduced complex I activity when normalized to citrate synthase activity in the brain

♀ • however, mice exhibit normal citrate synthase activity and normalized respiratory chain complex activity in the heart

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurodegeneration with brain iron accumulation 5		DOID:0110739	OMIM:300894	J:307284