Phenotypes Associated with This Genotype

Genotype
MGI:3721938

• Allelic Composition: Tg(CMV-IghvaD11)DCat/0; Tg(CMV-IgkvaD11)ACat/0
• Genetic Background: involves: C57BL/6 * SJL

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

Dilation of lateral ventricles and cholinergic deficit in aged Tg(CMV-IghvaD11)DCat/0 Tg(CMV-IgkvaD11)ACat/0 mice

behavior/neurological

abnormal object recognition memory ( J:62713 , J:212312 )

• aged mice show an impairment in an object recognition test (J:62713)

• 6 month old mice do not preferentially explore the new object during an object recognition test, spending an equal time exploring the new and the old object (J:212312)

abnormal spatial learning ( J:79946 )

• when given a new learning test following the retention test, mice show a deficit in transfer of learning capacity to a new situation compared to controls

impaired spatial learning ( J:62713 )

• although mice initially show normal learning curves in the radial maze of spatial learning, when tested at day 44, mice make significantly more errors than at day 14, and in a subsequent transfer test in which mice are exposed to a different disposition of the baits, mice show a decrease in ability to transfer their learning capacity to a new situation

abnormal long-term spatial reference memory ( J:79946 )

• when retested 31 days after initial training period, mice do not retain level of performance initial acquired with learning

abnormal spatial working memory ( J:79946 )

• in a radial maze test, mice show working memory errors

impaired coordination ( J:79946 )

• mice show marked impairment in coordination and fatigability assessed by the rotarod test

abnormal limb posture ( J:79946 )

• adult mice show abnormal hind limb position when walking or suspended by tail

abnormal gait ( J:79946 )

• adults display waddling gait due to abnormal hind limb position; mice walk on tiptoes of hind feet

increased thermal nociceptive threshold ( J:79946 )

• adult transgenic mice show increased latency in hot plate test

growth/size/body

decreased body weight ( J:79946 )

• mice appear normal but body weight is slightly decreased by 25% compared to littermates

hematopoietic system

increased splenocyte apoptosis ( J:79946 )

• transgenic mice have 3-fold more apoptotic cells in the spleen compared to controls

abnormal splenic cell ratio ( J:79946 )

• in adults, number of viable splenocytes in transgenic spleens is dramatically lower than in controls; proportion of IgG-positive cells is reduced while IgD-positive cells are slightly increased

immune system

increased splenocyte apoptosis ( J:79946 )

• transgenic mice have 3-fold more apoptotic cells in the spleen compared to controls

abnormal splenic cell ratio ( J:79946 )

• in adults, number of viable splenocytes in transgenic spleens is dramatically lower than in controls; proportion of IgG-positive cells is reduced while IgD-positive cells are slightly increased

muscle

abnormal skeletal muscle fiber morphology ( J:79946 )

• fibers show an irregular shape

decreased skeletal muscle fiber diameter ( J:79946 )

• fibers show a decreased cross-sectional area

decreased skeletal muscle mass ( J:79946 )

• at 2 months, significant reduction of the mass (atrophy) of longitudinal dorsal muscles and the flexor and abducent muscles of the hind limbs is observed in adults, but not in mice 2-30 days postnatal

nervous system

increased neuron apoptosis ( J:79946 )

• majority of neurons in lumbar DRG have pyknotic nuclei

amyloid beta deposits ( J:62713 , J:212312 )

• amyloid plaques are seen in the cortex, the neostriatum, the hippocampus, and other areas of the brain of aged mice (J:62713)

• plaques occupy a significant portion of the entorhinal cortex, with an amyloid burden equal to 21% of the total surface (J:62713)

abnormal sympathetic system morphology ( J:79946 )

• innervating fibers in the spleen are scattered throughout germinal center and marginal zone, without reaching the central artery

abnormal superior cervical ganglion morphology ( J:79946 )

• cells are greatly reduced in size (157-193 um² vs 218-311 um² in controls) at 2 months

small superior cervical ganglion ( J:79946 , J:212312 )

• markedly smaller at 2 months of age compared to controls (J:79946)

• size of the superior cervical ganglion is decreased due to extensive shrinkage of cell body (J:212312)

abnormal brain morphology ( J:62713 )

• free nerve growth factor in the brain of aged mice is at least 50% lower than in controls

dilated lateral ventricle ( J:62713 )

• dilation of the lateral ventricles in aged (15-18 months) mice

abnormal hippocampal mossy fiber morphology ( J:79946 )

• extent of CA3 mossy fibers is markedly reduced at 2 months

hippocampus atrophy ( J:62713 )

• atrophy of the hippocampus

• surface of the hippocampus is decreased

abnormal cerebral cortex morphology ( J:62713 )

• atrophy of the cerebral cortex, with a 34% reduction in the number of neurons in the frontal cortex

• DNA fragmentation, indicative of apoptosis, is seen in the cortex of aged mice

thin cerebral cortex ( J:62713 )

• cortical thickness is reduced in frontal areas of aged mice

neurofibrillary tangles ( J:62713 )

• neurofibrillary tangles in cortical and hippocampal neurons of aged mice

tau protein deposits ( J:62713 , J:212312 )

• aged mice show insoluble and hyperphosphorylated tau in neuronal and glial cells in the cortex and hippocampus (J:62713)

• phosphorylated-tau immunoreactivity is mainly located in the neuronal cell bodies or in apical dendrites (J:212312)

abnormal cholinergic neuron morphology ( J:62713 , J:79946 , J:212312 )

• total number of basal forebrain cholinergic neurons in aged mice shows an overall reduction of 60% and a 93% decrease in the medial septum (J:62713)

• number of choline acetyl transferase ChAT neurons in basal forebrain and hippocampus is reduced in adult animals relative to controls (J:79946)

• cell bodies of ChAT-positive fibers projecting to cortex and hippocampus show marked shrinkage (J:79946)

• decrease in the number of ChAT-positive cholinergic neurons in the medial septum and diagonal band of Broca as early as 2 months of age (J:212312)

abnormal neurite morphology ( J:62713 )

• dystrophic neurites in the cortex of aged mice

abnormal lumbar dorsal root ganglion morphology ( J:79946 )

• neuron size with respect to cell body size is dramatically reduced with median size of 425 um² in controls vs 75 um² in transgenic mice at 2 months

neurodegeneration ( J:62713 )

• progressive neurodegeneration

skeleton

scoliosis ( J:79946 )

• mice often develop scoliosis of the back

cellular

increased neuron apoptosis ( J:79946 )

• majority of neurons in lumbar DRG have pyknotic nuclei

increased splenocyte apoptosis ( J:79946 )

• transgenic mice have 3-fold more apoptotic cells in the spleen compared to controls

homeostasis/metabolism

amyloidosis ( J:79946 )

• amyloid deposits are seen in sarcoplasm of skeletal muscle

amyloid beta deposits ( J:62713 , J:212312 )

• amyloid plaques are seen in the cortex, the neostriatum, the hippocampus, and other areas of the brain of aged mice (J:62713)

• plaques occupy a significant portion of the entorhinal cortex, with an amyloid burden equal to 21% of the total surface (J:62713)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:62713