Phenotypes Associated with This Genotype

Genotype
MGI:3606654

• Allelic Composition: Csf2^tm1Mlg/Csf2^tm1Mlg
• Genetic Background: involves: 129S2/SvPas

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

mortality/aging ( J:17978 )

N • homozygotes obtained at the expected Mendelian frequencies are fertile and clinically healthy up to at least 1 year of age

hematopoietic system

hematopoietic system phenotype ( J:17978 )

N • homozygotes exhibit normal steady-state hematopoiesis with normal numbers of peripheral blood cells, bone marrow progenitors, and tissue hematopoietic populations, including splenic dendritic cells

N • notably, mutant marrow is able to reconstitute lethally irradiated mutant recipients

abnormal alveolar macrophage morphology ( J:17978 )

• mutant alveolar macrophages display aberrant morphology, including significant accumulation of surfactant lipids and proteins

• however, no significant reduction of alveolar macrophages is observed

immune system

abnormal alveolar macrophage morphology ( J:17978 )

• mutant alveolar macrophages display aberrant morphology, including significant accumulation of surfactant lipids and proteins

• however, no significant reduction of alveolar macrophages is observed

lymphoid hyperplasia ( J:17978 )

• homozygotes develop extensive pulmonary lymphoid hyperplasia around both airways and veins

• lymphoid hyperplasia is characterized by the presence of B220⁺, CD4⁺ and CD8⁺ cells, in the absence of a detectable underlying infection

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:148120 )

• resistant to experimental autoimmune encephalomyelitis

• myelin oligodendrocyte glycoprotein immunized mice show reduced IL-2 and Interferon-gamma recall response

• Ly-6^hi bone marrow precursor cells fail to expand in actively immunized mice as they do in controls

respiratory system

abnormal lung morphology ( J:17978 )

• 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

• similarly, the bronchoalveolar lavage is significantly enriched in SP-A, -B, and -C as well as in nonreducing oligomers of SP-A

• however, no accumulation of mature SP-A or its precursor is detected within type II pneumocytes

abnormal alveolar macrophage morphology ( J:17978 )

• mutant alveolar macrophages display aberrant morphology, including significant accumulation of surfactant lipids and proteins

• however, no significant reduction of alveolar macrophages is observed

abnormal pulmonary alveolus morphology ( J:17978 )

• by 2 months, all homozygotes exhibit early alveolar proteinosis, with amorphous, acellular, eosinophilic material scattered in alveolar spaces

• progressive surfactant lipid and protein accumulation, identified by the presence of tubular myelin and multilamellated structures, becomes widespread at >7 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary alveolar proteinosis		DOID:12120	OMIM:265120 OMIM:300770 OMIM:610913 OMIM:610921 OMIM:614370	J:17978