Phenotypes associated with this allele

• Allele Symbol: Chrnb2^tm1Jpc
• Allele Name: targeted mutation 1, Jean-Pierre Changeux
• Allele ID: MGI:1926253
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chrnb2^tm1Jpc/Chrnb2^tm1Jpc	B6.129P2-Chrnb2^tm1Jpc	MGI:3843521
hm2	Chrnb2^tm1Jpc/Chrnb2^tm1Jpc	involves: 129P2/OlaHsd	MGI:5318689
hm3	Chrnb2^tm1Jpc/Chrnb2^tm1Jpc	involves: 129P2/OlaHsd * C57BL/6	MGI:5318693
hm4	Chrnb2^tm1Jpc/Chrnb2^tm1Jpc	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3843507
hm5	Chrnb2^tm1Jpc/Chrnb2^tm1Jpc	involves: 129P2/OlaHsd * C57BL/6J	MGI:5318688

Genotype
MGI:3843521

hm1

• Allelic Composition: Chrnb2^tm1Jpc/Chrnb2^tm1Jpc
• Genetic Background: B6.129P2-Chrnb2^tm1Jpc

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

behavior/neurological

decreased chemically-elicited antinociception ( J:54505 )

• mutant mice do not show an antinociceptive response to the hot plate test at any dose of nicotine, whereas control mice show a dose-dependent antinociceptive response

• in contrast, nicotine causes a reduced but not absent dose-dependent analgesia in the tail flick test in mutant mice

nervous system

abnormal brain morphology ( J:77377 )

abnormal superior colliculus morphology ( J:77377 )

• ipsilateral projections from the retina are more extended

• dense innervation of the superior colliculus and the stratum griseum superficiale

• distribution of contralateral projections from the retina is unaffected

abnormal lateral geniculate nucleus morphology ( J:77377 )

• contralateral retinogeniculate projections cover the entire dorsal lateral nucleus rather than just the caudo-dorsal distribution found in controls

• ipsilateral retinogeniculate projections remain in the dorso-medial region

• retinogeniculate projections remain intermixed at 9 days of age when projections are segregating in controls and at 30 days

• binocular visual cortex is extended about 39%

abnormal nervous system electrophysiology ( J:109772 )

• spontaneous firing rate of dorsal lateral geniculate nucleus cells is higher than in controls

• neurons are more visually responsive

• shorter latencies and better response at higher temporal frequencies

abnormal nicotine-mediated receptor currents ( J:54505 )

• patch-clamp recordings indicate a loss of nicotine -elicited currents in serotonergic neurons in the raphe nucleus and thalamic neurons from mutant mice

• however, neurons in the superficial layers of the dorsal horn of the spinal cord continue to show a nicotine-elicited, dose-dependent augmentation of the frequency of post-synaptic currents

vision/eye

decreased visual acuity ( J:77377 )

• visual acuity reduced by a factor of two

immune system

decreased B cell number ( J:112766 )

• decreased numbers in bone marrow but not in spleen

hematopoietic system

decreased B cell number ( J:112766 )

• decreased numbers in bone marrow but not in spleen

Genotype
MGI:5318689

hm2

• Allelic Composition: Chrnb2^tm1Jpc/Chrnb2^tm1Jpc
• Genetic Background: involves: 129P2/OlaHsd

nervous system

abnormal lateral geniculate nucleus morphology ( J:139123 )

• ipsilateral retinogeniculate projections remain widespread in the dorsal lateral geniculate through 12 days of age

vision/eye

vision/eye phenotype ( J:139123 )

N • periodic retinal discharges are present as early as 2 days of age in Multi Electrode Recordings

abnormal eye electrophysiology ( J:139123 )

• wave and spike frequencies are greater than controls

• retinal firing frequency is increased

• increased burst frequency

• higher interspike intervals between bursts, lower percent of time cells are firing at greater than 10 Hz

• retinal waves not regulated by nicotinic acetylcholine receptors as is true for controls

• beta-glycerrhetinic acid (gap junction blocker) decreases wave frequency in mutants but not in controls

respiratory system

respiratory system phenotype ( J:102005 )

N • breathing parameters are more or less normal at 8 days of age

abnormal tidal volume ( J:102005 )

• tidal volume is increased post hypoxia relative to controls at 2 days of age

increased tidal volume ( J:102005 )

• at 2 days of age

apnea ( J:102005 )

• periods of apnea are shorter in duration than for controls

abnormal pulmonary ventilation ( J:102005 )

• peak ventilation response to hypoxia is significantly lower than for controls at 2 days but similar to controls at 8 days

• ventilation decline during hypoxia is less than for controls at both 2 and 8 days

increased pulmonary ventilation ( J:102005 )

• 16% larger ventilation values at 2 days of age than for controls

homeostasis/metabolism

decreased susceptibility to injury ( J:102005 )

• latency to arouse after hypoxia is shorter than for controls at 2 days of age but similar to controls at 8 days

• movements during hypoxia and post hypoxia fail to increase as they do in controls

behavior/neurological

abnormal behavior ( J:99880 )

• mutants exhibit alterations of behavioral flexibility and adaptive behaviors coupled with unimpaired memory and anxiety

enhanced spatial learning ( J:99880 )

• mutants exhibit improved spatial learning in a modified cross maze with a food reward, learning the task more rapidly and reaching the goal more quickly than wild-type mice

• however, mutants do not exhibit memory or recognition impairments

abnormal response to novelty ( J:99880 )

• mutants do not show sensitization to novelty and do not react to drastic changes of maze configuration

abnormal response to new environment ( J:99880 )

• mutants do not adapt their displacements over time in the open field as the environment becomes more familiar as in wild-type mice which adapt their displacements from fast navigation at the periphery of an open field to slow displacements toward the center of the arena indicating lack of exploratory interest

• mutants exhibit different exploratory behavior than wild-type when two objects are placed in the environment, showing an absence of the reorganization of the transitions between sequences of actions seen in wild-type mice, indicating that mutants do not exhibit the adaptive processes of becoming familiar with the environment

• mutants, however do not differ in the time spent in the anxiogenic area of the light/dark device or for the number of transitions between both compartments, indicating normal anxiety level

abnormal social investigation ( J:99880 )

• when faced with a social intruder of the same sex, mutants exhibit a higher rate of approach behaviors and lower rates of escape behaviors compared to wild-type mice, indicating disturbed social-interaction showing enhanced social interactions and an impaired capacity for interrupting ongoing behaviors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
attention deficit hyperactivity disorder		DOID:1094	OMIM:143465 OMIM:608903 OMIM:608904 OMIM:608905 OMIM:608906 OMIM:612311 OMIM:612312	J:99880
autism spectrum disorder		DOID:0060041		J:99880

Genotype
MGI:5318693

hm3

• Allelic Composition: Chrnb2^tm1Jpc/Chrnb2^tm1Jpc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:103908 )

N • IgM levels of preimmune serum are little altered from control levels

decreased B cell number ( J:103908 )

• number of IgG secreting cells is reduced

abnormal immune system physiology ( J:103908 )

increased B cell proliferation ( J:103908 )

• elevated proliferation in response to antiCD40 which is inhibited by nicotine

abnormal immunoglobulin level ( J:103908 )

increased IgG level ( J:103908 )

• increased IgG response to cytochrome c

• level remains elevated for 6 months after primary immunization

decreased immunoglobulin level ( J:103908 )

• significantly reduced preimmune serum Ig levels

hematopoietic system

increased B cell proliferation ( J:103908 )

• elevated proliferation in response to antiCD40 which is inhibited by nicotine

decreased B cell number ( J:103908 )

• number of IgG secreting cells is reduced

abnormal immunoglobulin level ( J:103908 )

increased IgG level ( J:103908 )

• increased IgG response to cytochrome c

• level remains elevated for 6 months after primary immunization

decreased immunoglobulin level ( J:103908 )

• significantly reduced preimmune serum Ig levels

cellular

increased B cell proliferation ( J:103908 )

• elevated proliferation in response to antiCD40 which is inhibited by nicotine

Genotype
MGI:3843507

hm4

• Allelic Composition: Chrnb2^tm1Jpc/Chrnb2^tm1Jpc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

behavior/neurological

behavior/neurological phenotype ( J:23256 )

N • spontaneous locomotor activity is not significantly different in mutant and control mice

N • spatial learning and memory is not significantly different in mutant and control mice, as assayed by both the hidden platform and visible platform Morris water maze test

N • mice do not differ from controls in the ability to respond to pain; flinch, vocalization and jump response to foot shock is similar in mutant and control mice

impaired passive avoidance behavior ( J:23256 )

• basal levels of passive avoidance bahavior are similar in mutant and control mice; however, nicotine treatment in control mice results in increased retention latency while no effect is seen in the mutant mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:23256 )

N • mutant mice do not exhibit differences in heart rate or basal body temperature

nervous system

abnormal brain morphology ( J:23256 )

• nicotine binding sites are completely abolished in the brain of mutant mice

abnormal nicotine-mediated receptor currents ( J:23256 )

• whole cell recordings of anterior thalamic neurons derived from mutant mice show that these neurons fail to evoke current in response to nicotine

Genotype
MGI:5318688

hm5

• Allelic Composition: Chrnb2^tm1Jpc/Chrnb2^tm1Jpc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

hematopoietic system

myeloid hyperplasia ( J:140280 )

• increased numbers of early myeloid cells in bone marrow

decreased erythroblast number ( J:140280 )

• fewer mature erythroid cells (normoblasts) found in bone marrow

immune system

myeloid hyperplasia ( J:140280 )

• increased numbers of early myeloid cells in bone marrow