Phenotypes Associated with This Genotype

Genotype
MGI:6192446

• Allelic Composition: Hprt1^tm1(MAPT)Dph/Y
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

behavior/neurological

behavior/neurological phenotype ( J:263643 )

♂N • swimming during probe trial in Morris water maze test ability from age 8 months

♂N • olfactory memory and function at age 8 months

♂N • anxiety behavior at age 8 months

impaired spatial learning ( J:263643 )

♂ • increased escape latency at day 4 in Morris water maze test from age 8 months

♂ • increased swim distance at day 4 in Morris water maze test from age 8 months

♂ • reduced occupancy of target quadrant during probe trial in Morris water maze test at age 8 months

♂ • reduced latency in target quadrant during probe trial in Morris water maze test from age 8 months

limb grasping ( J:263643 )

♂ • clasping by retraction of either hindlimbs or all four limbs

♂ • in of 5% of mice at age 4 months, 25% at 56 months

impaired coordination ( J:263643 )

♂ • latency to fall reduces progressively with age in rotarod test

decreased grip strength ( J:263643 )

♂ • no increase in hindlimbs up to age 8 months (versus increase with age in wildtype)

♂ • decrease in hindlimbs after age 8 months

♂ • in forelimbs

paresis ( J:263643 )

♂ • in all mice by age 18 months

muscle

abnormal skeletal muscle fiber morphology ( J:263643 )

♂ • fibrous endomysial connective tissue and some split fibers in absence of inflammatory infiltration

♂ • altered distribution of fiber size at age 16 months: presence of numerous small rounded fibers

skeletal muscle fiber degeneration ( J:263643 )

♂ • multiple internalized nuclei fibers in quadriceps and latissimus muscle at age 8 and 16 months

♂ • altered distribution of fiber size at age 16 months: presence of numerous small rounded fibers

nervous system

abnormal hippocampus morphology ( J:263643 )

♂ • tangle-like structures containing misfolded, phosphorylated tau (Mapt) protein in hippocampal neurons by age 14-16 months

♂ • astrocyte morphology at age 14 months

abnormal hippocampus physiology ( J:263643 )

♂ • loss of releasable synaptic vesicles in hippocampal neurons as indicated by 65% reduction in synapsin 1 (Syn1) levels at age 14 months

♂ • synaptic vesicle endocytosis in hippocampal neurons as indicated by normal levels of synaptophysin (Syp)

skeleton

kyphosis ( J:263643 )

♂ • kyphotic index (KI) of 4.5 (equal to wildtype) at age 4 months, 3.4 at 8 months and 2.9 at 14 months

homeostasis/metabolism

abnormal autophagy ( J:263643 )

♂ • impaired lysosome-mediated degradation in hippocampus/associated cortex at age 14 months

cellular

abnormal autophagy ( J:263643 )

♂ • impaired lysosome-mediated degradation in hippocampus/associated cortex at age 14 months

mortality/aging

premature death ( J:263643 )

♂ • reduced lifespan: 717 days median survival (versus 788 days for wildtype)

growth/size/body

growth/size/body region phenotype ( J:263643 )

♂N • body weight at age 18 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tauopathy		DOID:680		J:263643