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GERMAN MOUSE CLINIC, Martin Hrab ě de Angelis , Director

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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  1. 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

  2. Body Composition (qNMR)

  3. Body Composition (qNMR)

  4. Body Composition (qNMR) – Only Young

  5. Energy Metabolism: Results Indirect calorimetry

  6. Energy Metabolism: Results

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Behaviour: OF Results Forward locomotion No significant genotype effects on locomotor activity

  16. Behaviour: OF Results Vertical locomotion No genotype effect on rearing activity

  17. Behaviour: OF Results Anxiety-related behaviour No genotype effects on centre time

  18. Behaviour: Acoustic Startle Reactivity Increased ASR by the female mutant mice

  19. Behaviour: Prepulse Inhibition No genotype effect on PPI

  20. Neurology: SHIRPA-Results Nodifference in SHIRPA parameters Locomotoractivitymeasuredasthenumbersofsquarescrossed in thefirst 30 seconds after transferintothevievingarena.

  21. Neurology: Results No difference in grip strength

  22. 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

  23. Neurology: Results No difference in mean latencies, usual improvement over trials, But slightly more often falling

  24. Nociception: Results Hotplate Test Type ofreactionon hotplate

  25. 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)

  26. Cardiovascular: Results Echocardiography

  27. Cardiovascular: Results Electrocardiography

  28. Cardiovascular: Results Electrocardiography * * *

  29. Eye: Results Scheimpflug Imaging Duf1220 control

  30. Eye: Results Scheimpflug Imaging

  31. Eye: Results Virtual Drum (vision test)

  32. Levels of Immunoglobulins in Blood Plasma

  33. Levels of Immunoglobulins in Blood Plasma [µg/ml]

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

  35. 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

  36. 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.

  37. 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

  38. 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.

  39. TEWL Measurement

  40. Lung Function: Results

  41. Pathology: Results Organ Weight

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

  43. Pathology: Results Overview

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