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GERMAN MOUSE CLINIC, Martin Hrab ě de Angelis , Director PowerPoint PPT Presentation


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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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GERMAN MOUSE CLINIC, Martin Hrab ě de Angelis , Director

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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


Body Composition (qNMR)


Body Composition (qNMR)


Body Composition (qNMR) – Only Young


Energy Metabolism: Results

Indirect calorimetry


Energy Metabolism: Results


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.


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.


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


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


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


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


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


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.


Behaviour: OF Results

Forward locomotion

No significant genotype effects on locomotor activity


Behaviour: OF Results

Vertical locomotion

No genotype effect on rearing activity


Behaviour: OF Results

Anxiety-related behaviour

No genotype effects on centre time


Behaviour: Acoustic Startle Reactivity

Increased ASR by the female mutant mice


Behaviour: Prepulse Inhibition

No genotype effect on PPI


Neurology: SHIRPA-Results

Nodifference in SHIRPA parameters

Locomotoractivitymeasuredasthenumbersofsquarescrossed in thefirst 30 seconds after transferintothevievingarena.


Neurology: Results

No difference in grip strength


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


Neurology: Results

No difference in mean latencies, usual improvement over trials,

But slightly more often falling


Nociception: Results

Hotplate Test

Type ofreactionon hotplate


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)


Cardiovascular: Results Echocardiography


Cardiovascular: Results Electrocardiography


Cardiovascular: Results Electrocardiography

*

*

*


Eye: Results

Scheimpflug Imaging

Duf1220

control


Eye: Results

Scheimpflug Imaging


Eye: Results

Virtual Drum (vision test)


Levels of Immunoglobulins in Blood Plasma


Levels of Immunoglobulins in Blood Plasma [µg/ml]


Frequencies of Leukocyte Subsets in Blood [% of respective parent gate]


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


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.


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


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.


TEWL Measurement


Lung Function: Results


Pathology: Results Organ Weight


Pathology: Results Organ Weight

  • No statistically significant difference of total and normalized heart weight was detected comparing mutant and control mice.


Pathology: Results Overview


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