Phenotypes Associated with This Genotype

Genotype
MGI:3819267

• Allelic Composition: Chrna7^tm1Bay/Chrna7^tm1Bay
• Genetic Background: B6.129S7-Chrna7^tm1Bay/J

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

reproductive system

reproductive system phenotype ( J:92540 , J:115434 )

N • female homozygotes have normal ovaries and enter puberty at the expected age, with no significant differences in the onset of vaginal opening or cornification relative to wild-type or heterozygous control females (J:92540)

N • male homozygotes are fertile and exhibit an apparently normal mating behavior (J:92540)

N • testicular weight, total sperm number, and sperm morphology appear normal (J:115434)

asthenozoospermia ( J:115434 )

♂ • mutant sperm initially appear to swim normally but fail to maintain progressive forward motility

♂ • only few mutant sperm retain rapid swimming velocities and display hyperactivated swimming patterns following in vitro capacitation

♂ • many nonmotile sperm exhibit a quivering head and midpiece but no forward movement, confirming that cells are alive

♂ • however, no significant differences in sperm viability, senescence rate or spontaneous acrosome reaction rate are observed between mutant and wild-type sperm before and after capacitation

prolonged estrous cycle ( J:92540 )

♀ • female homozygotes show asynchronous, prolonged estrous cycles, with an average cycle length of 7.1 0.68 days relative to wild-type and heterozygous females (4.3 0.19 and 4.3 0.10 days, respectively)

♀ • the extent of asynchrony is variable within the mutant female population, but for a given animal, the average cycle length tends to remain stable at young mature ages (4-6 months) and middle ages (10-14 months)

♀ • all female homozygotes eventually complete an estrous cycle, and may achieve pregnancy but with a smaller number of surviving pups

reduced female fertility ( J:92540 )

♀ • the number of live births is significantly less from matings of female homozygotes with either heterozygous (4.5 2.12) or homozygous (3.7 0.53) mutant males in comparison to matings of heterozygous females and males (7.34 0.04) and matings of heterozygous females and homozygous mutant males (7.1 0.40)

decreased litter size ( J:92540 )

• litters born to homozygous mutant females are significantly smaller than those born to heterozygous females regardless of the male genotype

nervous system

abnormal brain interneuron morphology ( J:214099 )

• development of parvalbumin-positive GABAergic interneurons is disrupted in cortical cultures

• NMDA receptor expression is reduced in cortical GABAergic interneurons of cortical cultures

• development and maturation of cortical parvalbumin-positive basket cells is impaired in cortical cultures

• parvalbumin and GAD67 levels are reduced in the soma of parvalbumin-positive GABAergic interneurons

• GABAAalpha1 levels are reduced in parvalbumin-positive GABAergic interneurons in the prefrontal cortex

abnormal cerebral cortex morphology ( J:214099 )

• cortical levels of GABAergic makers (parvalbumin, glutamic acid decarboxylase 65/67 (GAD65/67) and the alpha1 subunit of GABAA receptors) are decreased during late postnatal development and adulthood

abnormal cerebral cortex pyramidal cell morphology ( J:214099 )

• GABAAalpha1 levels are reduced in pyramidal neurons of the prefrontal cortex

decreased CNS synapse formation ( J:214099 )

• marker analysis indicates that cortical GABAergic synapse formation is impaired in prefrontal cortex and in cortical cultures

• formation of parvalbumin- and GAD65-positive perisomatic synapses is impaired in cortical cultures

abnormal GABAergic neuron morphology ( J:214099 )

• levels of markers of GABAergic maturation are reduced in the neocortex indicating that cortical parvalbumin GABAergic development is impaired

abnormal GABAergic neuron physiology ( J:214099 )

• cortical GABAergic synaptic defects in the prefrontal cortex and in cortical cultures

abnormal GABA-mediated receptor currents ( J:214099 )

• cultured cortical pyramidal neurons show a reduction in sIPSC frequency and current decay time, but not amplitude, indicating reduced GABAergic neurotransmission

behavior/neurological

impaired spatial working memory ( J:123663 )

♂ • in the delayed matching-to-place task of the Morris water maze, mutants take longer to find the hidden platform than controls, indicating a minor impairment in working/episodic memory

♂ • however, mice show normal latency to enter the central zone of the open field, normal elevated plus maze behavior, and no differences in swim speed or thigmotaxic behavior

taste/olfaction

impaired olfaction ( J:166638 )

• mice exhibit deficits in detecting or discriminating chemically-related odors

cellular

asthenozoospermia ( J:115434 )

♂ • mutant sperm initially appear to swim normally but fail to maintain progressive forward motility

♂ • only few mutant sperm retain rapid swimming velocities and display hyperactivated swimming patterns following in vitro capacitation

♂ • many nonmotile sperm exhibit a quivering head and midpiece but no forward movement, confirming that cells are alive

♂ • however, no significant differences in sperm viability, senescence rate or spontaneous acrosome reaction rate are observed between mutant and wild-type sperm before and after capacitation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:214099