cardiovascular system phenotype

• abnormal aorta collagen fibril morphology
  • collagen bundles are loosely arranged and/or disintegrated
  (MGI Ref ID J:84697)
  • slight reduction in alpha1(VIII)
  (MGI Ref ID J:84697)
  • collagen fibrils are thinner and more variable in diameter
  (MGI Ref ID J:84697)
  • collagen distribution in the adventitia of the aorta is more diffuse than it is in controls where it is present in discrete layers
  (MGI Ref ID J:84697)
  • fibrillar collagen alpha1(III) is completely abolished
  (MGI Ref ID J:84697)
  • fibrillar collagen alpha1(I) reduced by about 16.5%
  (MGI Ref ID J:84697)

• abnormal aorta elastic fiber morphology
  • elastin layers are variably thinner than in controls
  (MGI Ref ID J:84697)

hematopoietic system phenotype

• abnormal alveolar macrophage morphology
  • however, no significant reduction of alveolar macrophages is observed
  (MGI Ref ID J:17978)
  • mutant alveolar macrophages display aberrant morphology, including significant accumulation of surfactant lipids and proteins
  (MGI Ref ID J:17978)

mammalian phenotype

• hematopoietic system phenotype
  • Normal - homozygotes exhibit normal steady-state hematopoiesis with normal numbers of peripheral blood cells, bone marrow progenitors, and tissue hematopoietic populations, including splenic dendritic cells
  (MGI Ref ID J:17978)
  • Normal - notably, mutant marrow is able to reconstitute lethally irradiated mutant recipients
  (MGI Ref ID J:17978)

• mortality/aging
  • Normal - homozygotes obtained at the expected Mendelian frequencies are fertile and clinically healthy up to at least 1 year of age
  (MGI Ref ID J:17978)

respiratory system phenotype

• abnormal lung morphology
  • lung lavage fluid obtained from homozygotes displays an 8-fold increase in total protein content, with significant accumulation of surfactant proteins SP-A and SP-B
  (MGI Ref ID J:17978)
  • however, no accumulation of mature SP-A or its precursor is detected within type II pneumocytes
  (MGI Ref ID J:17978)
  • similarly, the bronchoalveolar lavage is significantly enriched in SP-A, -B, and -C as well as in nonreducing oligomers of SP-A
  (MGI Ref ID J:17978)

• abnormal alveolar macrophage morphology
  • mutant alveolar macrophages display aberrant morphology, including significant accumulation of surfactant lipids and proteins
  (MGI Ref ID J:17978)
  • however, no significant reduction of alveolar macrophages is observed
  (MGI Ref ID J:17978)

• abnormal pulmonary alveolus morphology
  • progressive surfactant lipid and protein accumulation, identified by the presence of tubular myelin and multilamellated structures, becomes widespread at >7 months
  (MGI Ref ID J:17978)
  • by 2 months, all homozygotes exhibit early alveolar proteinosis, with amorphous, acellular, eosinophilic material scattered in alveolar spaces
  (MGI Ref ID J:17978)

immune system phenotype

• abnormal alveolar macrophage morphology
  • mutant alveolar macrophages display aberrant morphology, including significant accumulation of surfactant lipids and proteins
  (MGI Ref ID J:17978)
  • however, no significant reduction of alveolar macrophages is observed
  (MGI Ref ID J:17978)

• lymphoid hyperplasia
  • lymphoid hyperplasia is characterized by the presence of B220⁺, CD4⁺ and CD8⁺ cells, in the absence of a detectable underlying infection
  (MGI Ref ID J:17978)
  • homozygotes develop extensive pulmonary lymphoid hyperplasia around both airways and veins
  (MGI Ref ID J:17978)

• decreased susceptibility to experimental autoimmune encephalomyelitis
  • Ly-6^hi bone marrow precursor cells fail to expand in actively immunized mice as they do in controls
  (MGI Ref ID J:148120)
  • myelin oligodendrocyte glycoprotein immunized mice show reduced IL-2 and Interferon-gamma recall response
  (MGI Ref ID J:148120)
  • resistant to experimental autoimmune encephalomyelitis
  (MGI Ref ID J:148120)

adipose tissue phenotype

• abnormal mesenteric fat pad morphology
  • significant reduction in macrophage in mesenteric fat when on a high fat diet
  (MGI Ref ID J:142440)
  • expression of IL-1beta, TNF-alpha, and CCL3 in mesenteric fat are significantly reduced when on a high fat diet
  (MGI Ref ID J:142440)

• increased fat cell size
  • mean adipocyte size is significantly larger on a high fat diet
  (MGI Ref ID J:142440)

growth/size/body region phenotype

• increased body weight
  • increased body weight on a high fat diet
  (MGI Ref ID J:142440)

homeostasis/metabolism phenotype

• abnormal circulating glucose level
  • greater glucose infusion is necessary to maintain glucose levels during a glucose clamp
  (MGI Ref ID J:142440)
  • greater overall glucose clearance
  (MGI Ref ID J:142440)

• decreased circulating insulin level
  • lower insulin levels at baseline and during a glucose clamp
  (MGI Ref ID J:142440)

• enhanced gluconeogenesis
  • endogenous glucose production is greater at baseline and during glucose clamp
  (MGI Ref ID J:142440)

endocrine/exocrine gland phenotype

• abnormal pancreatic islet morphology
  • large lymphoid aggregates surround but do not penetrate many islets
  (MGI Ref ID J:145518)

growth/size/body region phenotype

• increased body weight
  • gain significantly more weight than controls but are similar in body length
  (MGI Ref ID J:102499)

homeostasis/metabolism phenotype

• increased circulating triglyceride level
  • 88.4mg/dl in males compared to 28.8mg/dl in controls
  (MGI Ref ID J:102499)

• decreased energy expenditure
  • Normal - activity pattern normal
  (MGI Ref ID J:102499)
  • reduced energy expenditure in both males and females but a greater reduction in females
  (MGI Ref ID J:102499)

• increased circulating leptin level
  (MGI Ref ID J:102499)

• abnormal lipid level
  (MGI Ref ID J:102499)

• increased circulating free fatty acids level
  • 0.19 mmol/l in males compared to 0.08 mmol/l in controls
  (MGI Ref ID J:102499)

• increased circulating glucose level
  • modestly increased
  (MGI Ref ID J:145518)

integument phenotype

• increased subcutaneous adipose tissue amount
  (MGI Ref ID J:102499)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - activity pattern normal
  (MGI Ref ID J:102499)

adipose tissue phenotype

• increased gonadal fat pad weight
  • perigonadal fat pad weights are increased in both males and females
  (MGI Ref ID J:102499)

• increased total body fat amount
  • 278% increase in males accounting for 78% of increased body weight
  (MGI Ref ID J:102499)
  • Normal - lean body mass is unaffected
  (MGI Ref ID J:102499)
  • 174% increase in females accounting for 63 % of increased body weight
  (MGI Ref ID J:102499)

• increased abdominal adipose tissue amount
  • visceral fat is increased
  (MGI Ref ID J:102499)

• increased mesenteric fat pad weight
  • in females
  (MGI Ref ID J:102499)

• abnormal abdominal fat pad morphology
  (MGI Ref ID J:102499)

• increased subcutaneous adipose tissue amount
  (MGI Ref ID J:102499)

behavior/neurological phenotype

• increased food intake
  • increased food intake in males but not in females
  (MGI Ref ID J:102499)