Phenotypes for Timp3 MGI:3056101 MGI Mouse

increased susceptibility to induced morbidity/mortality ( J:112033 )

• mutants subjected to cardiac pressure overload by aortic-banding exhibit higher mortality than wild-type

premature death ( J:71609 )

• homozygotes of a mixed genetic background are viable, fertile and of normal size and weight; normal viability and fertility are also observed after backcrossing into a C57BL/6, CD-1, or FVB background

• however, homozygotes of a mixed genetic background exhibit a mean survival of 67.3 8.4 wks vs 137 wks in wild-type

• in addition, homozygotes of a mixed genetic background show sex-specific differences in survival, with the mean survival age for mutant males being 62 6.4 wks vs 72 7.6 wks for females

lethargy ( J:71609 )

• beginning at 13 months, some homozygotes become overtly sick and lethargic

hunched posture ( J:71609 )

• at 13 months, some homozygotes exhibit a hunched posture

cellular phenotype ( J:71609 )

N	• mutant lungs do not exhibit abnormal apoptosis at any age examined (2 weeks to aged) • in situ zymography shows increased matrix metalloproteinase activity in lungs from aged homozygotes • in vitro, mutant fibroblast cultures show enhanced degradation of ECM molecules

endocrine/exocrine gland phenotype ( J:71609 )

N	• young adult homozygotes show no microscopic abnormalities in mammary tissue

renal/urinary system phenotype ( J:71609 )

N	• young adult homozygotes show no microscopic abnormalities in kidney tissue

pulmonary edema ( J:112033 )

• mutants subjected to cardiac pressure overload develop pulmonary edema at 6 weeks of aortic-banding compared to wild-type that develop it at 12 weeks

abnormal pulmonary alveolus morphology ( J:71609 )

• lungs from aged homozygotes show disorganization of collagen fibrils in the alveolar interstitium; however, no elevated inflammatory cell infiltration or fibrosis is observed

overexpanded pulmonary alveolus ( J:71609 )

• as early as 2 weeks, mutant lungs show a progressive (age-dependent) increase in the average space between opposing alveolar walls

• mutant alveoli are not homogeneously enlarged; however, the average alveolar size is significantly increased at all ages examined (2 weeks to aged)

• in aged homozygotes, the average alveolar size is increased by ~50%

• in aged homozygotes, lungs show a significant decline in hydroxy-proline content, consistent with alveolar enlargement; this decline is not statistically significant at 4-8 months

abnormal bronchiole morphology ( J:71609 )

• lungs from aged homozygotes show enhanced degradation of collagen in the peribronchiolar space

• overall, lung collagen content is reduced by about 32% in aged mutant mice

abnormal respiratory system physiology ( J:71609 )

• at ~52 weeks, male homozygotes show a 18% reduction in carbon monoxide uptake (a test of lung function); at this age, female homozygotes display a 13% reduction

• at 8 weeks, no significant difference in carbon monoxide uptake is observed

respiratory distress ( J:71609 )

• at 13 months, some homozygotes display labored breathing involving abdominal accessory muscles

cardiac hypertrophy ( J:112033 )

• mutants subjected to cardiac pressure overload show greater cardiac hypertrophy (both eccentric and concentric) while wild-type controls show only concentric hypertrophy and to a smaller extent

abnormal heart left ventricle morphology ( J:112033 )

• mutants subjected to cardiac pressure overload exhibit higher levels of apoptosis in the left ventricle at 6 weeks of aortic-banding than controls

dilated heart left ventricle ( J:112033 )

• mutants subjected to cardiac pressure overload show greater left ventricular dilatation in the absence of reduced left ventricle wall thickness compared to wild-type

cardiac fibrosis ( J:112033 )

• mutants subjected to cardiac pressure overload develop increased fibrosis than seen in wild-type at 6 weeks of aortic-banding

dilated cardiomyopathy ( J:112033 )

• mutants subjected to cardiac pressure overload by aortic-banding develop dilated cardiomyopathy

decreased cardiac muscle contractility ( J:112033 )

• mutants subjected to cardiac pressure overload by aortic-banding exhibit earlier onset of impaired contractility

increased response of heart to induced stress ( J:112033 )

• mutants subjected to cardiac pressure overload by aortic-banding exhibit earlier onset of cardiac dysfunction (1 week after banding compared to 6 weeks in wild-type), including LV dilation, reduced aortic outflow velocity, cardiac contractility, and velocity of circumferential fiber shortening, lower LV developed pressure, higher end-diastolic pressure and suppressed LV peak rates of pressure-rise and pressure-fall (+/- dP/dt)

congestive heart failure ( J:112033 )

• unlike wildtype, develop congestive heart failure 6 weeks after pressure overload by aortic-banding