Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1 locus.
Disruption of the murine Mop3 (also known as Bmal1 or Arntl) locus results in a loss of behavioral and molecular circadian rhythms. Although Mop3 null mice do not display anomalies in early development, they do display reduced activity as they age. In an effort to explain this decreased activity, we characterized the physiological and anatomical changes that occurred with age. We observed that Mop3 null mice display an increased mortality after 26 weeks of age and a phenotype best described as a progressive noninflammatory arthropathy. Although little pathology is observed prior to 11 weeks of age, by 35 weeks of age essentially all Mop3 null animals develop joint ankylosis due to flowing ossification of ligaments and tendons and almost complete immobilization of weight-bearing and nonweight-bearing joints. This pathology appears to explain the decreased activity of Mop3 null mice and suggests that MOP3 is an inhibitor of ligament and tendon ossification.
Bunger
Maureen K
MK
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
Walisser
Jacqueline A
JA
Sullivan
Ruth
R
Manley
Paul A
PA
Moran
Susan M
SM
Kalscheur
Vicki L
VL
Colman
Ricki J
RJ
Bradfield
Christopher A
CA
D056930:ARNTL Transcription Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001842:Bone and Bones / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D007592:Joint Diseases / Q000235:genetics* / Q000473:pathology; D008022:Ligaments / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009999:Ossification, Heterotopic / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D013710:Tendons / Q000473:pathology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015431:Weight Loss
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; C538961:Bmal1 protein, mouse