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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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German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

Body Composition (qNMR)


German mouse clinic martin hrab de angelis director

Body Composition (qNMR)


German mouse clinic martin hrab de angelis director

Body Composition (qNMR) – Only Young


German mouse clinic martin hrab de angelis director

Energy Metabolism: Results

Indirect calorimetry


German mouse clinic martin hrab de angelis director

Energy Metabolism: Results


German mouse clinic martin hrab de angelis director

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.


German mouse clinic martin hrab de angelis director

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.


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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.


German mouse clinic martin hrab de angelis director

Behaviour: OF Results

Forward locomotion

No significant genotype effects on locomotor activity


German mouse clinic martin hrab de angelis director

Behaviour: OF Results

Vertical locomotion

No genotype effect on rearing activity


German mouse clinic martin hrab de angelis director

Behaviour: OF Results

Anxiety-related behaviour

No genotype effects on centre time


German mouse clinic martin hrab de angelis director

Behaviour: Acoustic Startle Reactivity

Increased ASR by the female mutant mice


German mouse clinic martin hrab de angelis director

Behaviour: Prepulse Inhibition

No genotype effect on PPI


German mouse clinic martin hrab de angelis director

Neurology: SHIRPA-Results

Nodifference in SHIRPA parameters

Locomotoractivitymeasuredasthenumbersofsquarescrossed in thefirst 30 seconds after transferintothevievingarena.


German mouse clinic martin hrab de angelis director

Neurology: Results

No difference in grip strength


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

Neurology: Results

No difference in mean latencies, usual improvement over trials,

But slightly more often falling


German mouse clinic martin hrab de angelis director

Nociception: Results

Hotplate Test

Type ofreactionon hotplate


German mouse clinic martin hrab de angelis director

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)


German mouse clinic martin hrab de angelis director

Cardiovascular: Results Echocardiography


German mouse clinic martin hrab de angelis director

Cardiovascular: Results Electrocardiography


German mouse clinic martin hrab de angelis director

Cardiovascular: Results Electrocardiography

*

*

*


German mouse clinic martin hrab de angelis director

Eye: Results

Scheimpflug Imaging

Duf1220

control


German mouse clinic martin hrab de angelis director

Eye: Results

Scheimpflug Imaging


German mouse clinic martin hrab de angelis director

Eye: Results

Virtual Drum (vision test)


German mouse clinic martin hrab de angelis director

Levels of Immunoglobulins in Blood Plasma


German mouse clinic martin hrab de angelis director

Levels of Immunoglobulins in Blood Plasma [µg/ml]


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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.


German mouse clinic martin hrab de angelis director

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


German mouse clinic martin hrab de angelis director

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.


German mouse clinic martin hrab de angelis director

TEWL Measurement


German mouse clinic martin hrab de angelis director

Lung Function: Results


German mouse clinic martin hrab de angelis director

Pathology: Results Organ Weight


German mouse clinic martin hrab de angelis director

Pathology: Results Organ Weight

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


German mouse clinic martin hrab de angelis director

Pathology: Results Overview


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