Phenotypes Associated with This Genotype

Genotype
MGI:3809583

• Allelic Composition: Tg(RCAN1)M9Mapr/?
• Genetic Background: involves: C57BL/6 * CBA

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

endocrine/exocrine glands

abnormal adrenal gland secretion ( J:132495 )

• reduced exocytosis in chromaffin cells when stimulated with 70mM potassium for 1 minute

• decreased amounts of catecholamine released for each fusion event involving vesicles and the cell membrane

• foot signals resulting from fusion pore formation decreased in height

• less neurotransmitter released per foot signal

behavior/neurological

abnormal object recognition memory ( J:184606 )

• mutants exhibit a deficit in non-spatial working memory, with mutants spending a lower percentage of time examining the novel object in the retention testing phase of a novel object recognition task

abnormal spatial learning ( J:184606 )

abnormal long-term spatial reference memory ( J:184606 )

• in the Morris water maze test, over 6 days of place discrimination training to learn the position of the submerged platform, mutants show slower escape latencies than wild-type mice

• when the hidden platform is removed and a probe trial is conducted on day 7 of a Morris water maze test, mutants spend less time in the target quadrant indicating that they did not learn the location of the platform

abnormal short-term spatial reference memory ( J:184606 )

• mutants do not display normal spontaneous alternation behavior in a Y-maze, indicating a deficit in short term memory

increased anxiety-related response ( J:184606 )

• while mutants spend a similar amount of time in the novel arm of a Y-maze as do controls, they rear more than controls, indicating increased anxiety

increased vertical activity ( J:184606 )

• mutants rear more times than controls in 30 min trials

cellular

abnormal neuron differentiation ( J:184606 )

• 53.3% reduction in the number of ldU-labeled neurons within the dentate gyrus, indicating a reduction in the formation of new terminally differentiated neurons within the dentate gyrus in adults

• subventricular zone-derived neurospheres produce a higher proportion of astrocytes (85.91 vs. 75.93%) and oligodendrocytes (2.25 vs. 1.45%) than wild-type neurospheres

• ability of cultured neural progenitor cells to generate neurons is reduced (17.9 vs. 10.98%)

nervous system

abnormal neuron differentiation ( J:184606 )

• 53.3% reduction in the number of ldU-labeled neurons within the dentate gyrus, indicating a reduction in the formation of new terminally differentiated neurons within the dentate gyrus in adults

• subventricular zone-derived neurospheres produce a higher proportion of astrocytes (85.91 vs. 75.93%) and oligodendrocytes (2.25 vs. 1.45%) than wild-type neurospheres

• ability of cultured neural progenitor cells to generate neurons is reduced (17.9 vs. 10.98%)

abnormal hippocampus morphology ( J:184606 )

• reduction in hippocampal volume

abnormal hippocampus CA1 region morphology ( J:184606 )

• mutants show a trend towards a reduction in the total number and density of neurons in the CA1 region of the hippocampus

abnormal dentate gyrus morphology ( J:184606 )

• significant decrease in the size of the dentate gyrus, with a 33% reduction in volume

• 40% decrease in neurons in the dentate gyrus, however the density of neurons within the region is not different from wild-type

abnormal dendritic spine morphology ( J:184606 )

• apical and basal dendrites of CA1 hippocampal pyramidal neurons exhibit a 39.2% and 28.8% decrease in spine density, respectively

decreased neuron number ( J:184606 )

• reduction in the total number of neurons in the dentate gyrus and a trend towards a reduction of neurons in the CA1 region of the hippocampus

abnormal nervous system electrophysiology ( J:184606 )

• mutants exhibit a decrease is overall level of glutamate-evoked intracellular calcium in hippocampal neurons indicating impaired glutamate-evoked post-synaptic calcium transients

reduced long-term potentiation ( J:184606 )

• mutants fail to maintain long-term potentiation in hippocampal slices, showing a shorter average decay time constant and a reduction in the mean amplitude of responses to high frequency stimulation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Down syndrome		DOID:14250	OMIM:190685	J:184606