Phenotypes associated with this allele

• Allele Symbol: Csf2^tm1Mlg
• Allele Name: targeted mutation 1, Richard C Mulligan
• Allele ID: MGI:1930996
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Csf2^tm1Mlg/Csf2^tm1Mlg	B6.129S2-Csf2^tm1Mlg	MGI:5431915
hm2	Csf2^tm1Mlg/Csf2^tm1Mlg	involves: 129S2/SvPas	MGI:3606654
hm3	Csf2^tm1Mlg/Csf2^tm1Mlg	involves: 129S2/SvPas * BALB/c	MGI:5431911
hm4	Csf2^tm1Mlg/Csf2^tm1Mlg	involves: 129S2/SvPas * C57BL/6	MGI:5431916
cx5	Csf2^tm1Mlg/Csf2^tm1Mlg Il3^tm1Glli/Il3^tm1Glli	B6.129S2-Csf2^tm1Mlg Il3^tm1Glli	MGI:5431917
cx6	Csf2^tm1Mlg/Csf2^tm1Mlg Ifng^tm1Ts/Ifng^tm1Ts Il3^tm1Glli/Il3^tm1Glli	B6.129S-Csf2^tm1Mlg Il3^tm1Glli Ifng^tm1TsIfng^tm1Ts	MGI:5431918

Genotype
MGI:5431915

hm1

• Allelic Composition: Csf2^tm1Mlg/Csf2^tm1Mlg
• Genetic Background: B6.129S2-Csf2^tm1Mlg

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

growth/size/body

increased body weight ( J:102499 )

• gain significantly more weight than controls but are similar in body length

adipose tissue

increased subcutaneous adipose tissue amount ( J:102499 )

increased abdominal adipose tissue amount ( J:102499 )

• visceral fat is increased

increased total body fat amount ( J:102499 )

• 278% increase in males accounting for 78% of increased body weight

• 174% increase in females accounting for 63 % of increased body weight

• lean body mass is unaffected

abnormal abdominal fat pad morphology ( J:102499 )

increased gonadal fat pad weight ( J:102499 )

• perigonadal fat pad weights are increased in both males and females

increased mesenteric fat pad weight ( J:102499 )

♀ • in females

homeostasis/metabolism

increased circulating glucose level ( J:145518 )

• modestly increased

increased circulating leptin level ( J:102499 )

decreased energy expenditure ( J:102499 )

• reduced energy expenditure in both males and females but a greater reduction in females

• activity pattern normal

abnormal lipid level ( J:102499 )

increased circulating free fatty acids level ( J:102499 )

♂ • 0.19 mmol/l in males compared to 0.08 mmol/l in controls

increased circulating triglyceride level ( J:102499 )

♂ • 88.4mg/dl in males compared to 28.8mg/dl in controls

behavior/neurological

behavior/neurological phenotype ( J:102499 )

N • activity pattern normal

increased food intake ( J:102499 )

♂ • increased food intake in males but not in females

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:145518 )

• large lymphoid aggregates surround but do not penetrate many islets

integument

increased subcutaneous adipose tissue amount ( J:102499 )

Genotype
MGI:3606654

hm2

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

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

Genotype
MGI:5431911

hm3

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

cardiovascular system

abnormal aorta collagen fibril morphology ( 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

• collagen bundles are loosely arranged and/or disintegrated

• collagen fibrils are thinner and more variable in diameter

• fibrillar collagen alpha1(I) reduced by about 16.5%

• fibrillar collagen alpha1(III) is completely abolished

• slight reduction in alpha1(VIII)

abnormal aorta elastic fiber morphology ( J:84697 )

• elastin layers are variably thinner than in controls

Genotype
MGI:5431916

hm4

• Allelic Composition: Csf2^tm1Mlg/Csf2^tm1Mlg
• Genetic Background: involves: 129S2/SvPas * C57BL/6

growth/size/body

increased body weight ( J:142440 )

• increased body weight on a high fat diet

adipose tissue

increased fat cell size ( J:142440 )

• mean adipocyte size is significantly larger on a high fat diet

abnormal mesenteric fat pad morphology ( J:142440 )

• significant reduction in macrophage in mesenteric fat when on a high fat diet

• expression of IL-1beta, TNF-alpha, and CCL3 in mesenteric fat are significantly reduced when on a high fat diet

homeostasis/metabolism

abnormal circulating glucose level ( J:142440 )

• greater glucose infusion is necessary to maintain glucose levels during a glucose clamp

• greater overall glucose clearance

decreased circulating insulin level ( J:142440 )

• lower insulin levels at baseline and during a glucose clamp

enhanced gluconeogenesis ( J:142440 )

• endogenous glucose production is greater at baseline and during glucose clamp

Genotype
MGI:5431917

cx5

• Allelic Composition: Csf2^tm1Mlg/Csf2^tm1Mlg; Il3^tm1Glli/Il3^tm1Glli
• Genetic Background: B6.129S2-Csf2^tm1Mlg Il3^tm1Glli

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:145518 )

• large lymphoid aggregates surround and penetrate many islets

• islets are reduced in size

decreased pancreatic beta cell number ( J:145518 )

• reduced number of insulin secreting beta cells

homeostasis/metabolism

hyperglycemia ( J:145518 )

• fasting hyperglycemia in most but not all 8 month old mice

• significantly increased peak blood sugar after glucose challenge

impaired glucose tolerance ( J:145518 )

• significantly increased peak blood sugar after glucose challenge

Genotype
MGI:5431918

cx6

• Allelic Composition: Csf2^tm1Mlg/Csf2^tm1Mlg; Ifng^tm1Ts/Ifng^tm1Ts; Il3^tm1Glli/Il3^tm1Glli
• Genetic Background: B6.129S-Csf2^tm1Mlg Il3^tm1Glli Ifng^tm1TsIfng^tm1Ts

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:145518 )

• islet adenomas

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:145518 )

N • significantly reduced fasting blood sugar, to levels similar to controls

N • improved glucose tolerance

neoplasm

increased pituitary adenoma incidence ( J:145518 )

• islet adenomas

nervous system

increased pituitary adenoma incidence ( J:145518 )

• islet adenomas