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Collaboration with Majesta O‘Bleness , Jonathon Keeney and James Sikela Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus/USA. Mouse Line DUF1220KO (Domain Deletion from PDE4DIP : phosphodiesterase 4D interacting protein ( myomegalin )).

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Presentation Transcript
slide1
Collaborationwith

MajestaO‘Bleness, Jonathon Keeney andJames Sikela

BiochemistryandMolecularGenetics

University of Colorado Anschutz Medical Campus/USA

Mouse Line DUF1220KO(Domain Deletion from PDE4DIP: phosphodiesterase 4D interacting protein (myomegalin))

GERMAN MOUSE CLINIC,

Martin Hraběde Angelis, Director

slide5
Energy Metabolism: Results

Indirect calorimetry

slide7
Energy Metabolism: Conclusions

Duf1220 ko mice were hyperactive both regarding locomotor activity as well as rearing behavior. The hyperactivity had no major effects on energy metabolism related parameters.

slide8
Results IpGTT

Fasting induced body mass loss vs. Initial body weight

DUF1220ko mutant mice

Body mass loss due to overnight food withdrawal mainly depended

on initial body mass.

No clear genotype effect was detected for body mass loss.

slide9
Results IpGTT

Plasma glucose concentration [mmol/l] during IpGTT

We see a trend towards higher AUC values in male mutants, but the differences are quite small with largely overlapping ranges. Therefore this result might be accidental.

AUC 0-30

AUC 30-120

slide10
Clinical Chemistry Results, Fasting

Means, standard deviation and p-values calculated by a linear model(parameter ~ genotype * sex)

Fourfemaleanimals – 1 control, 3 mutant – not testedbecauseoftoolowbodyweight.

Glucose

slide11
Clinical Chemistry Results

Means, standard deviation and p-values calculated by a linear model(parameter ~ genotype * sex)

One female Mut excluded ID 30264548 > severe kidney disease

Sodium

Chloride

Potassium

slide12
Clinical Chemistry: Results

Means, standard deviation and p-values calculated by a linear model (parameter ~ genotype * sex)

One female Mut excluded ID 30264548 > severe kidney disease

ALAT

ASAT

LDH

slide13
Clinical Chemistry: Results

Means, standard deviation and p-values calculated by a linear model (parameter ~ genotype * sex)

One female Mut excluded ID 30264548 > severe kidney disease

ALP

slide14
Hematology: Results

Means, standard deviation and p-values calculated by a linear model (parameter ~ genotype * sex)

Data of one animal excluded due to technical problems (30264526, male mutant)

No evidence of remarkable genotype-related differences.

slide15
Behaviour: OF Results

Forward locomotion

No significant genotype effects on locomotor activity

slide16
Behaviour: OF Results

Vertical locomotion

No genotype effect on rearing activity

slide17
Behaviour: OF Results

Anxiety-related behaviour

No genotype effects on centre time

slide18
Behaviour: Acoustic Startle Reactivity

Increased ASR by the female mutant mice

slide19
Behaviour: Prepulse Inhibition

No genotype effect on PPI

slide20
Neurology: SHIRPA-Results

Nodifference in SHIRPA parameters

Locomotoractivitymeasuredasthenumbersofsquarescrossed in thefirst 30 seconds after transferintothevievingarena.

slide21
Neurology: Results

No difference in grip strength

slide22
Neurology: Results

Since we are especially interested in mitochondria function we measure as a marker lactate levels in collaboration with the Clinical Chemistry Screen

No difference

White 2001, Sex Transm Infect 2001;77:158-173 doi:10.1136/sti.77.3.158

slide23
Neurology: Results

No difference in mean latencies, usual improvement over trials,

But slightly more often falling

slide24
Nociception: Results

Hotplate Test

Type ofreactionon hotplate

slide25
Dysmorphology: Results

Clickbox Test

BL6 background

  • become deaf

with age

0 = no reaction at all

1 = no Preyer reflex

2 = retarded reaction

3 = normal reaction

4 = strong reaction

5 = particularly strong reaction

  • no significance

(Fisher’s Exact test)

slide29
Eye: Results

Scheimpflug Imaging

Duf1220

control

slide30
Eye: Results

Scheimpflug Imaging

slide31
Eye: Results

Virtual Drum (vision test)

slide35
Frequencies of Leukocyte Subsets in Blood [% of all leukocytes]

Lower frequencies of T cells and a slightly lower CD4: CD8 T cell ratio in mutants of both sexes

slide36
IgE Results
  • Total plasma IgE in Duf1220KO mice (1st sample)

Median, first and third quartile and p-values calculated by a Wilcoxon rank-sum test.

slide37
IgE Results

Box plot of total plasma IgE in Duf1220KO mice ng/ml

No statistically significant differences in the IgE levels between control and mutants mice

slide38
TEWL Measurement

Box plot of transepidermal water loss (TEWL) [g/(m²h)] in Duf1220KOmice

Median, first and third quartile and p-values calculated by a Wilcoxon rank-sum test.

NO statistically significant differences in the TEWL levels between control and mutants male mice.

slide42
Pathology: Results Organ Weight
  • No statistically significant difference of total and normalized heart weight was detected comparing mutant and control mice.
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