Submitted on February 6, 2007
Accepted on May 23, 2007
Fgl2 deficiency causes neonatal death and cardiac dysfunction during embryonic and postnatal development in mice
Junwu Mu1, Dawei Qu1, Agata Bartczak2, M. James Phillips2, Justin Manuel2, Wei He2, Cheryl Koscik2, Michael Mendicino2, Li Zhang2, David A. Clark2, David R. Grant2, Peter H. Backx3, Gary A Levy4, and S. Lee Adamson5*
1 Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, Canada
2 the Multi-Organ Transplant Program of the University Health Network, Toronto, Canada
3 Medicine, United States; Physiology, United States; the Heart and Stroke/Richard Lewar Centre, United States; Cardiology, United States
4 Medicine, Toronto, Canada; the Multi-Organ Transplant Program of the University Health Network, Toronto, Canada
5 Departments of Obstetrics & Gynecology, United States; Physiology, United States; the Heart and Stroke/Richard Lewar Centre, United States; the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, United States
* To whom correspondence should be addressed. E-mail: adamson{at}mshri.on.ca.
We hypothesized that cardiac dysfunction was responsible for the high perinatal lethality that we previously reported in Fgl2 knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left ventricular (LV) cardiac structure and function during development in Fgl2 KO and wildtype (WT) mice. The only deaths observed between embryonic day 8.5 (E8.5; onset of heart beating) and postnatal day 28 (P28; weaning) were within 3 d after birth when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments suggested death was due to acute congestive cardiac failure without evidence of valvular or other obvious cardiac structural abnormalities. Heart rates in Fgl2 KO embryos were significantly reduced at E8.5 and E17.5 and irregular heart rhythms were significantly more common in Fgl2 KOs (21/26) than in WTs (2/21) at E13.5. Indices of systolic and/or diastolic cardiac function were also abnormal in KOs at E13.5, E17.5, and in postnatal mice studied at P1, and in surviving KOs to P28. M-mode analysis showed no difference in LV diastolic chamber dimension although posterior wall thickness was thinner at P7 and P28 in Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious structural cardiac defects but is associated with a high incidence of neonatal death as well as contractile dysfunction and rhythm abnormalities during embryonic and postnatal development in mice.
