Phenotypes associated with this allele

• Allele Symbol: Adcy8^tm1Ljm
• Allele Name: targeted mutation 1, Louis J Muglia
• Allele ID: MGI:2176596
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adcy8^tm1Ljm/Adcy8^tm1Ljm	involves: 129 * Black Swiss	MGI:3622150
hm2	Adcy8^tm1Ljm/Adcy8^tm1Ljm	involves: 129S1/Sv * 129X1/SvJ	MGI:3809556
hm3	Adcy8^tm1Ljm/Adcy8^tm1Ljm	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:2176597
cx4	Adcy1^tm1Drs/Adcy1^tm1Drs Adcy8^tm1Ljm/Adcy8^tm1Ljm	involves: 129 * Black Swiss	MGI:3622151
cx5	Adcy1^tm1Drs/Adcy1^tm1Drs Adcy8^tm1Ljm/Adcy8^tm1Ljm	involves: 129/Sv * C57BL/6	MGI:3622142

Genotype
MGI:3622150

hm1

• Allelic Composition: Adcy8^tm1Ljm/Adcy8^tm1Ljm
• Genetic Background: involves: 129 * Black Swiss

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

behavior/neurological

increased chemical nociceptive threshold ( J:107678 )

• phase 2 responses to formalin injection are decreased in mutants

Genotype
MGI:3809556

hm2

• Allelic Composition: Adcy8^tm1Ljm/Adcy8^tm1Ljm
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal single cell response ( J:164682 )

• following transfection with dominant negative or constitutively active CREB, locus coeruleus neurons fail to exhibit alterations in firing unlike similarly treated wild-type or Adcy1^tm1Drs neurons

• following chronic morphine treatment and withdrawal, locus coeruleus neurons fail to exhibit an increase in firing wild-type or Adcy1^tm1Drs neurons

Genotype
MGI:2176597

hm3

• Allelic Composition: Adcy8^tm1Ljm/Adcy8^tm1Ljm
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss

behavior/neurological

decreased anxiety-related response ( J:63173 )

• mutants take less time to leave a perimeter outlined on a large table top over two test sessions

• on an elevated plus-maze, mutants spend more time in open arms and travel a greater distance than controls, indicating reduced anxiety

• mutants exhibit fewer closed arm SAPs and head dips, take less time to leave the center area to first enter an arm, and exhibit more head dips over the side of the open arms, all indicating reduced anxiety

growth/size/body

decreased body size ( J:63173 )

• females gain weight until 30 days of age, at which point they remain 10-15% smaller

• males gain weight similarly to wild type up until age 45, at which point they grow more slowly between 45 and 92 days of age, after which weight differences are not significant

• however, food intake is normal

nervous system

absent long-term depression ( J:63173 )

• no measurable LTD after low frequency stimulation in hippocampal slices derived from homozygous mice

homeostasis/metabolism

abnormal corticosterone level ( J:63173 )

• mutants subjected to chronic restraint stress exhibit elevated basal corticosterone level before their final restraint compared with wild-type

abnormal enzyme/coenzyme activity ( J:63173 )

• calcium-stimulated adenylyl cyclase activity is almost entirely absent from the hypothalamus, olfactory bulb, thalamus, and brainstem and is reduced 40-50% in the hippocampus

taste/olfaction

taste/olfaction phenotype ( J:63173 )

N • normal odorant sensing

Genotype
MGI:3622151

cx4

• Allelic Composition: Adcy1^tm1Drs/Adcy1^tm1Drs; Adcy8^tm1Ljm/Adcy8^tm1Ljm
• Genetic Background: involves: 129 * Black Swiss

behavior/neurological

hyporesponsive to tactile stimuli ( J:107678 )

• at 1 and 3 days after injection of complete Freunds' adjuvant into the hindpaw, wild-type mice withdraw their hindpaw in response to stimulation of the ipsilateral or contralateral hind paw, but in double knockouts this allodynia is completely abolished

• after nerve injury, reduction in mechanical sensitivity in double knockouts was reduced of abolished compared with wild-type

increased chemical nociceptive threshold ( J:107678 )

• phase 2 responses to formalin injection (10-55 minutes after injection) are decreased in mutants, to a greater extent than in Adcy8 knockouts

• phase 3 responses to formalin injection (55-120 minutes following) are decreased in mutants relative to wild-type

Genotype
MGI:3622142

cx5

• Allelic Composition: Adcy1^tm1Drs/Adcy1^tm1Drs; Adcy8^tm1Ljm/Adcy8^tm1Ljm
• Genetic Background: involves: 129/Sv * C57BL/6

behavior/neurological

impaired passive avoidance behavior ( J:57343 )

• double knockout animals exhibit passive avoidance learning but display a memory deficit as early as 30 minutes after training; lower latencies are also apparent 24 hours and 8 days after training compared with single knockouts or wild-type; latencies are comparable to controls after forskolin treatment of CA1 of the hippocampus15 minutes before training

abnormal contextual conditioning behavior ( J:57343 )

• double knockouts exhibit a decrease in freezing behavior compared to wild-type after 8 days in a contextual learning paradigm

nervous system

reduced long-term potentiation ( J:57343 )

• sustained L-LTP could not be generated in hippocampal slices from double knockout mice; the fEPSP slope exhibited a significant decrement at all times after tetanus; LTP dropped off after 80 minutes compared to 3 hours in each of the single knockouts