Phenotypes associated with this allele

• Allele Symbol: Fbn1⁺
• Allele Name: wild type
• Allele ID: MGI:2430500
• Summary: 28 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Fbn1^Tsk/Fbn1^+	B10.D2/(58N)Sn	MGI:3604814
ht2	Fbn1^Tsk/Fbn1^+	B6.Cg-Fbn1^Tsk	MGI:3619520
ht3	Fbn1^Tsk/Fbn1^+	B6.Cg-Fbn1^Tsk +/+ Bloc1s6^pa/JKcc	MGI:4365578
ht4	Fbn1^em1Chop/Fbn1^+	C57BL/6-Fbn1^em1Chop	MGI:6400541
ht5	Fbn1^em1(IMPC)H/Fbn1^+	C57BL/6NTac-Fbn1^em1(IMPC)H/H	MGI:7414890
ht6	Fbn1^tm1Hcd/Fbn1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3690327
ht7	Fbn1^tm3.1Hcd/Fbn1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5558880
ht8	Fbn1^tm2.1Hcd/Fbn1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5558879
ht9	Fbn1^tm1Lper/Fbn1^+	involves: 129/Sv * C57BL/6 * CD-1	MGI:4880671
ht10	Fbn1^tm1Lper/Fbn1^+	involves: 129/Sv * CD-1	MGI:4880670
ht11	Fbn1^tm1.2Lysa/Fbn1^+	involves: C57BL/6	MGI:4839089
ht12	Fbn1^tm3.2Lysa/Fbn1^+	Not Specified	MGI:5313384
cx13	Fbn1^Tsk Bloc1s6^+/Fbn1^+ Bloc1s6^pa	B6.Cg-Fbn1^Tsk +/+ Bloc1s6^pa/J	MGI:3721113
cx14	Fbn1^tm3Rmz/Fbn1^+ Fbn2^tm1Rmz/Fbn2^tm1Rmz	involves: 129	MGI:3652417
cx15	Fbn1^tm1Hcd/Fbn1^+ Tgfb2^tm1Doe/Tgfb2^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5444488
cx16	Fbn1^tm3.1Hcd/Fbn1^+ Itgb3^tm1Hyn/Itgb3^+	involves: 129S * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5558883
cx17	Fbn1^tm2.1Hcd/Fbn1^+ Itgb3^tm1Hyn/Itgb3^+	involves: 129S * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5558881
cx18	Fbn1^Tsk/Fbn1^+ Stat6^tm1Gru/Stat6^tm1Gru	involves: 129S2/SvPas * C57BL/10 * DBA/2	MGI:5301099
cx19	Fbn1^Tsk/Fbn1^+ Tgfb1^tm1N/Tgfb1^+	involves: 129S/SvEv * C57BL/6J * C57BL/10 * DBA/2	MGI:3800678
cx20	Fbn1^Tsk/Fbn1^+ Tgfb1^tm1N/Tgfb1^tm1N	involves: 129S/SvEv * C57BL/6J * C57BL/10 * DBA/2	MGI:3800993
cx21	Fbn1^tm1.2Lysa/Fbn1^+ Fbn2^tm1Rmz/Fbn2^tm1Rmz	involves: 129/Sv * C57BL/6	MGI:4839090
cx22	Fbn1^Tsk/Fbn1^+ Il4ra^tm1Sz/Il4ra^+	involves: BALB/cJ * C57BL/6J * C57BL/10 * DBA/2	MGI:3800676
cx23	Fbn1^Tsk/Fbn1^+ Il4ra^tm1Sz/Il4ra^tm1Sz	involves: BALB/cJ * C57BL/6J * C57BL/10 * DBA/2	MGI:3800675
cx24	Fbn1^Tsk/Fbn1^+ Tg(Tcra2C,Tcrb2C)1Dlo/?	involves: C57BL/10 * DBA/2	MGI:5301105
cx25	Fbn1^Tsk/Fbn1^+ Tg(TcraH-Y,TcrbH-Y)71Vbo/?	involves: C57BL/10 * DBA/2	MGI:5301104
cx26	Fbn1^Tsk/Fbn1^+ Il4^tm1Nnt/Il4^tm1Nnt	involves: C57BL/6 * C57BL/10 * DBA/2	MGI:5301103
cx27	Fbn1^Tsk/Fbn1^+ Kit^W/Kit^+	involves: C57BL/6 * C57BL/10 * DBA/2 * WB/ReJ	MGI:3619906
cx28	Fbn1^Tsk/Fbn1^+ Kit^W/Kit^W-v	involves: C57BL/6 * C57BL/10 * DBA/2 * WB/ReJ	MGI:3619905

Genotype
MGI:3604814

ht1

• Allelic Composition: Fbn1^Tsk/Fbn1⁺
• Genetic Background: B10.D2/(58N)Sn

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

skeleton

abnormal skeleton morphology ( J:5629 )

• excessive growth of connective tissue and skeleton

• increase in skeletal size, however body weight is not increased

enlarged cranium ( J:5629 )

• longer skull

long mandible ( J:5629 )

• longer and wider mandible

abnormal tendon morphology ( J:5629 )

• tail and ankle tendons are sgnificantly smaller in size

• in older mice, some tendons show degenerative changes with increased cellularity and decreased amount of collagen

abnormal tendon sheath morphology ( J:5629 )

• in the tail, tendon size reduction is often associated with hyperplasia of the tendon sheath or with accumulation of fluid with the sheath

• ankle tendons show hyperplasia of the tendon sheath as well as hyperplasia of the loose connective tissue between the tendons

increased length of long bones ( J:5629 )

• long bones and girdles are about 5% larger

abnormal pelvic girdle bone morphology ( J:5629 )

• pelvic bone is about 10% larger

long ribs ( J:5629 )

• longer ribs

enlarged lumbar vertebrae ( J:5629 )

• enlarged in both length and width

abnormal cartilage morphology ( J:5629 )

• increase in growth of cartilage

• longer length of the ear cartilage

abnormal tracheal cartilage morphology ( J:5629 )

• longer length of the fourth tracheal ring

abnormal costal cartilage morphology ( J:5629 )

• costal cartilages are elongated and more bowed than normal

cardiovascular system

dilated heart atrium ( J:5629 )

enlarged heart ( J:5629 )

cardiac hypertrophy ( J:32931 )

dilated heart right ventricle ( J:5629 )

• enlarged but not as much as the auricles

respiratory system

abnormal lung morphology ( J:5629 )

• lungs become abnormally distended in enlarged thorax

emphysema ( J:5629 )

• vesicular emphysema

abnormal tracheal cartilage morphology ( J:5629 )

• longer length of the fourth tracheal ring

muscle

abnormal tendon morphology ( J:5629 )

• tail and ankle tendons are sgnificantly smaller in size

• in older mice, some tendons show degenerative changes with increased cellularity and decreased amount of collagen

abnormal tendon sheath morphology ( J:5629 )

• in the tail, tendon size reduction is often associated with hyperplasia of the tendon sheath or with accumulation of fluid with the sheath

• ankle tendons show hyperplasia of the tendon sheath as well as hyperplasia of the loose connective tissue between the tendons

behavior/neurological

hunched posture ( J:5629 )

• develop a pronounced hump in the shoulder region and hunched posture with age

craniofacial

enlarged cranium ( J:5629 )

• longer skull

long mandible ( J:5629 )

• longer and wider mandible

growth/size/body

enlarged heart ( J:5629 )

cardiac hypertrophy ( J:32931 )

enlarged thoracic cavity ( J:5629 )

• enlarged thorax causing distension of the thoracic viscera

integument

abnormal hypodermis morphology ( J:5629 , J:6273 )

• hyperplasia of the subcutaneous loose connective tissue (J:5629)

• in loose connective tissue, exhibit large accumulations of microfibrils in the intercellular space (J:5629)

• hypodermis is more lamellar (J:6273)

• fascicles of unusually thin collagen fibrils are found in scattered areas of the hypodermis (J:6273)

thick hypodermis ( J:6273 )

• hypodermis is substantially thicker

abnormal skin morphology ( J:6273 )

abnormal dermal layer morphology ( J:6273 )

• dermis fibroblasts often contain greatly distended rough endoplasmic reticulum cisternae

• collagen fibrils within the fascicles of the dermis are less ordered and the fascicles are thinner and more closely packed and appear to bend and twist more along their course

abnormal dermis papillary layer morphology ( J:6273 )

• fibrous organization of collagen fibrils is not distinctly visible in the hyalinized areas of the superficial dermis

thick dermal layer ( J:6273 )

• reticular dermis of skin is consistently thicker and often more cellular than that of wild-type

tight skin ( J:5629 , J:27521 , J:32931 )

• skin tightness is not seen at birth but develops during the first postnatal week (J:5629)

• caused by hyperplasia of subcutaneous loose connective tissue (J:27521)

• skin is firmly bound to subcutaneous and deep muscular tissue (J:32931)

• skin lacks normal pliability and elasticity (J:32931)

abnormal skin condition ( J:27521 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:21512

Genotype
MGI:3619520

ht2

• Allelic Composition: Fbn1^Tsk/Fbn1⁺
• Genetic Background: B6.Cg-Fbn1^Tsk

Fbn1^Tsk/Fbn1⁺ skin exhibits abnormal organization and distribution of microfibrillar arrays

respiratory system

lung inflammation ( J:6566 , J:30961 )

• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils in the interstitium (J:6566)

• increased numbers of alveolar macrophages and neutrophils in the interstitium (J:30961)

alveolitis ( J:6566 , J:15018 , J:30961 )

• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils within alveolar air spaces (J:6566)

• macrophage-neutrophil alveolitis is seen at 3 weeks of age, at a time when emphysematous lesions are not yet present (J:15018)

• exhibit alveolitis, with increased numbers of alveolar macrophages and neutrophils in the alveolar lumens (J:30961)

abnormal lung morphology ( J:30961 )

dilated pulmonary alveolar duct ( J:15018 , J:30961 )

• enlarged alveolar ducts are first seen at 3 weeks of age (J:15018)

• dilation of alveolar ducts (J:30961)

abnormal pulmonary alveolus morphology ( J:1326 , J:3934 , J:6566 , J:15018 , J:30961 )

• exhibit formation of bullae and subpleural cysts and fragmented elastin in alveolar walls (J:1326)

• enlargement of air spaces with numerous subpleural cysts and scattered bullae (J:6566)

• at 3 weeks of age, alveoli are flattened but not enlarged, however by 4-6 weeks af age, alveoli are enlarged (J:15018)

• thinning and destruction of alveolar walls (J:30961)

• numerous broken alveolar septa and bullous lesions (J:30961)

• alveoli are irregular in size, with most appearing enlarged (J:30961)

decreased pulmonary alveolus wall thickness ( J:30961 )

• thinning and destruction of alveolar walls

overexpanded pulmonary alveolus ( J:68448 , J:15018 , J:30961 )

• enlarged alveoli are 3 to 4 times larger than normal and show a histologic picture of emphysema (J:68448)

• develop enlarged alveoli between 4 and 6 weeks of age (J:15018)

• distension of many alveoli (J:30961)

abnormal pulmonary interalveolar septum morphology ( J:3934 )

• progressive destruction of alveolar septa and increase in collagen deposition in the septa that may result from repair of the lung destruction

abnormal alveolar pore morphology ( J:6566 , J:30961 )

• increase in the number and size of the pores of Kohn (J:6566)

• alveolar pores in septa are variable in size and increased in number (J:30961)

thick pulmonary interalveolar septum ( J:3934 )

• diffuse thickening of the septa not affected by emphysematous changes, resulting from a progressive increase in collagen

emphysema ( J:3934 , J:6566 , J:15018 )

• emphysematous lesions are seen at 4 weeks of age (J:15018)

abnormal bronchiole morphology ( J:30961 )

• dilation of bronchioles

increased total lung capacity ( J:6566 , J:30961 )

• increase in total lung capacity (J:30961)

increased lung compliance ( J:6566 , J:30961 )

• increase in lung compliance (J:30961)

immune system

abnormal uterine NK cell morphology ( J:1377 )

♀ • distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally

increased mast cell number ( J:8047 )

• increase in number and enhanced degree of degranulation of mast cells in the skin

increased susceptibility to type IV hypersensitivity reaction ( J:7185 )

• develop cell-mediated immunity to elastase-soluble murine lung peptides with age while delayed-type hypersensitivity responses to type I or type IV collagen are not detected

increased autoantibody level ( J:14166 , J:21987 )

• develop autoantibodies specific for scleroderma target antigens, with a bias toward the use of V_HJ558 genes and J_H2 and J_K2 segments (J:14166)

• develop anti-nucleolar antibodies and produce significantly higher titers of autoantibodies specific for scleroderma target antigens (topo I, RNA pol I, and Fc gamma R) (J:21987)

lung inflammation ( J:6566 , J:30961 )

• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils in the interstitium (J:6566)

• increased numbers of alveolar macrophages and neutrophils in the interstitium (J:30961)

alveolitis ( J:6566 , J:15018 , J:30961 )

• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils within alveolar air spaces (J:6566)

• macrophage-neutrophil alveolitis is seen at 3 weeks of age, at a time when emphysematous lesions are not yet present (J:15018)

• exhibit alveolitis, with increased numbers of alveolar macrophages and neutrophils in the alveolar lumens (J:30961)

hematopoietic system

abnormal uterine NK cell morphology ( J:1377 )

♀ • distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally

increased mast cell number ( J:8047 )

• increase in number and enhanced degree of degranulation of mast cells in the skin

cardiovascular system

abnormal aorta tunica adventitia morphology ( J:1326 )

• aorta exhibits hyperplasia of loose connective tissue in the adventitia

• collagen fibers in the aorta are increased and microfibrils surrounding elastin in the adventitia of the aorta are not clearly apparent

abnormal heart morphology ( J:17160 , J:24523 )

• 2.5-fold increase in type VI collagen content in myocardium (J:17160)

• collagen deposition is increased in the heart (J:24523)

• type I collagen is increased in the myocardium, perhaps due to reduced activity of negative regulatory sequence (J:24523)

abnormal heart right ventricle morphology ( J:20724 )

• increase in collagen content in the right ventricle at 3 months of age; however, by 16 months of age, collagen content returns to normal levels but there is a shift in collagen type due to an increase in type I collagen, and by 24 months of age, again see an increase in collagen content

heart right ventricle hypertrophy ( J:20724 )

• starts to develop at around 8 months of age

cardiac fibrosis ( J:1562 , J:24523 )

• thyroid hormone treatment decreases collagen synthesis and stimulates regression of cardiac fibrosis (J:1562)

• exhibit myocardial fibrosis (J:24523)

renal/urinary system

abnormal urinary bladder morphology ( J:3616 )

• 70% increase in collagen content and concentration in the bladder at 5-6 months of age

abnormal urinary bladder physiology ( J:3616 )

• functional bladder capacity appears to be greater

polyuria ( J:3616 )

• urinate larger volumes more frequently during the light cycle

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:29151 )

N • no aberrant bleeding time after tail vein nick

reproductive system

abnormal uterine NK cell morphology ( J:1377 )

♀ • distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally

integument

abnormal hypodermis morphology ( J:8047 )

• increase in width of the subcutaneous fibrous layer with increasing age

abnormal skin morphology ( J:7057 )

• significantly greater skin biopsy weights, however percent of water-fat is similar to wild-type

• hexosamine, uronic acid, and total glycosaminoglycan content is increased in skin

abnormal cutaneous collagen fibril morphology ( J:68448 )

• electron micrographs of skin show a predominance of abnormally small diameter collagen fibers and the skin shows abundant irregular and wavy collagen bundles

abnormal cutaneous microfibril morphology ( J:46405 )

• transmission electron microscopy of the upper dermis shows more prominent microfibrillar clusters, which often appear blurred and lacking a discernible striated pattern, but an absence of well-packed elastic fibrils

• although there is a morphologically normal population of skin microfibrils, approximately 45% of the skin microfibril population has abnromal periodic arrays of beads with indistinct filamentous interbeads and extended periodicity of 112 (+/-11) nm relative to 55 (+/-4) nm in normal microfibrils

• the abnormal skin microfibrils have an altered response to calcium chelation by EDTA, with diminished shortening of the periodicity of microfibrils and less prominant appearance of beading compared with control microfibrils, and the large microfibril aggregates fail to dissociate

thick skin ( J:68448 )

• skin is 228 um thick on average instead of the wildtype 132 um

skin fibrosis ( J:68448 , J:26096 )

• develop skin fibrosis which results originally from collagen I and III overexpression and later collagen VI overexpression (J:26096)

• unlike human scleroderma, fibrosis does not manifest Tgfb1 mRNA in areas of abnormal collagen deposition (J:26096)

abnormal skin physiology ( J:68448 , J:8140 )

• fibroblasts synthesize increased collagen both constitutively and in response to IL4 or TGFB, although IL13 does not increase fibroblast collagen synthesis (J:68448)

• cultured skin fibroblasts synthesize almost 5 times more Type I and Type III procollagen mRNA indicating production of excessive amounts of collagen (J:8140)

embryo

abnormal uterine NK cell morphology ( J:1377 )

♀ • distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally

endocrine/exocrine glands

abnormal uterine NK cell morphology ( J:1377 )

♀ • distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally

growth/size/body

heart right ventricle hypertrophy ( J:20724 )

• starts to develop at around 8 months of age

muscle

heart right ventricle hypertrophy ( J:20724 )

• starts to develop at around 8 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:30961
pulmonary emphysema		DOID:9675	OMIM:130700	J:30961 , J:1326 , J:6566 , J:15018 , J:68448
systemic scleroderma		DOID:418	OMIM:181750	J:7057 , J:21987 , J:7185 , J:8047

Genotype
MGI:4365578

ht3

• Allelic Composition: Fbn1^Tsk/Fbn1⁺
• Genetic Background: B6.Cg-Fbn1^Tsk +/+ Bloc1s6^pa/JKcc

cardiovascular system

abnormal aorta elastin content ( J:63844 )

• in 3 week old mice fragmentation of elastic lamellae is seen in van-Gieson stained histological sections of the ascending aorta

integument

abnormal dermal layer morphology ( J:63844 )

abnormal dermis reticular layer morphology ( J:63844 )

• Trichrome-stained sections of adult skin show loose connective tissue contains excessive collagen fibers tightly bound to the muscle layer

abnormal dermis reticular layer collagen network ( J:63844 )

• Trichrome-stained sections of adult skin show loose connective tissue contains excessive collagen fibers tightly bound to the muscle layer

Genotype
MGI:6400541

ht4

• Allelic Composition: Fbn1^em1Chop/Fbn1⁺
• Genetic Background: C57BL/6-Fbn1^em1Chop

growth/size/body

decreased body fat mass ( J:251851 )

abnormal postnatal growth/weight/body size ( J:251851 )

• mice show extreme leanness

decreased lean body mass ( J:251851 )

decreased body weight ( J:251851 )

• decrease in body weight already at weaning

decreased susceptibility to diet-induced obesity ( J:251851 )

• mice fed a high-fat diet are protected from obesity and diabetes

adipose tissue

decreased body fat mass ( J:251851 )

behavior/neurological

decreased food intake ( J:251851 )

• hypophagia

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:251851 )

• mice fed a high-fat diet are protected from obesity and diabetes

decreased circulating leptin level ( J:251851 )

• decrease in leptin levels in mice fed normal chow or a high-fat diet

decreased energy expenditure ( J:251851 )

• mice show a reduction in energy expenditure

• however, reduction in energy expenditure normalizes after feeding a high-fat diet

• however, no difference in respiratory exchange ratio is seen and heart rate, blood pressure, body temperature, and thyroid hormone axis are unaffected

nervous system

abnormal neuron physiology ( J:251851 )

• activity of agouti-related neuropeptide (AgRP+) neurons in the arcuate nucleus of the hypothalamus is lower as indicated by decreased firing frequency and resting membrane potential

• an overnight fast has no effect on activity of AgRP+ neurons compared to wild-type neurons which show increased activity

• ghrelin shows a decreased ability to activate AgRP+ neurons

• paraventricular nucleus of the hypothalamus (PVH) neurons show increased firing rate and resting membrane potential

Genotype
MGI:7414890

ht5

• Allelic Composition: Fbn1^em1(IMPC)H/Fbn1⁺
• Genetic Background: C57BL/6NTac-Fbn1^em1(IMPC)H/H

Data Sources

IMPC Data for Fbn1

growth/size/body

increased spleen weight ( J:211773 )

♂

IMPC - HAR

hematopoietic system

increased spleen weight ( J:211773 )

♂

IMPC - HAR

increased neutrophil cell number ( J:211773 )

♂

IMPC - HAR

increased mean platelet volume ( J:211773 )

♀

IMPC - HAR

decreased lymphocyte cell number ( J:211773 )

♂

IMPC - HAR

immune system

increased spleen weight ( J:211773 )

♂

IMPC - HAR

increased neutrophil cell number ( J:211773 )

♂

IMPC - HAR

decreased lymphocyte cell number ( J:211773 )

♂

IMPC - HAR

Genotype
MGI:3690327

ht6

• Allelic Composition: Fbn1^tm1Hcd/Fbn1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal aorta wall morphology ( J:91349 , J:188799 )

• progressive deterioration within the medial layer, with elastic fiber fragmentation and disarray of vascular smooth muscle cells begins around 2 months of age (J:91349)

• however, no intimal hyperplasia, aortic inflammation, or aortic dissection are detected and life span is similar to wild-type mice (J:91349)

abnormal aorta elastic fiber morphology ( J:91349 )

• progressive fragmentation of elastic fibers within the medial wall beginning around 2 months of age

• elastic fiber calcification is occasionally seen

increased aorta wall thickness ( J:94428 )

• gradual thickening of the wall due to excessive deposition of amorphous matrix and increase in the number of vascular smooth muscle cells

abnormal mitral valve cusp morphology ( J:94428 )

• progressive increase in leaflet length and thickness during postnatal development

• leaflet length and thickness are intermediate between homozygous mutant and wild-type mice

• cells display increased proliferation and reduced apoptosis

• in utero treatment with TGFB neutralizing antibodies at E14.5 and E17.5 rescues mitral valve morphology

mitral valve prolapse ( J:94428 )

• mitral valve prolapse and regurgitation at 9 months of age

increased heart left atrium size ( J:94428 )

• left atrium enlargement associated with mitral valve prolapse

increased heart left ventricle size ( J:94428 )

• left ventricle enlargement associated with mitral valve prolapse

mitral valve regurgitation ( J:94428 )

• mitral valve prolapse and regurgitation at 9 months of age

respiratory system

overexpanded pulmonary alveolus ( J:91349 )

• distal airspace widening without inflammation or tissue damage

skeleton

abnormal skeleton morphology ( J:91349 )

• gradual postnatal development of skeletal abnormalities similar to those in other hypomorphic mouse models of Marfan Syndrome

abnormal rib morphology ( J:91349 )

• postnatal overgrowth

kyphosis ( J:91349 )

• gradual postnatal development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:91349 , J:94428

Genotype
MGI:5558880

ht7

• Allelic Composition: Fbn1^tm3.1Hcd/Fbn1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

immune system

increased B cell number ( J:206074 )

• infiltration of activated B cells and plasma cells in the dermis

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased plasma cell number ( J:206074 )

• infiltration of activated B cells and plasma cells in the dermis

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

abnormal T-helper 1 cell morphology ( J:206074 )

• dermal polarization towards pro-inflammatory T helper cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

abnormal interleukin secretion ( J:206074 )

• increased IL9, IL13 and IL22 in CD3+ dermal cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased interleukin-13 secretion ( J:206074 )

• in CD3+ dermal cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased interleukin-9 secretion ( J:206074 )

• in CD3+ dermal cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased autoantibody level ( J:206074 )

• increased anti-nuclear and anti-topoisomerase I antibody levels

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased anti-nuclear antigen antibody level ( J:206074 )

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

integument

decreased subcutaneous adipose tissue amount ( J:206074 )

• by 3 months

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal cutaneous collagen fibril morphology ( J:206074 )

• increased by 1 month

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal dermal layer morphology ( J:206074 )

• disorganized and excessive microfibrillar aggregates in the dermis with sparsely distributed elastin

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

increased skin stiffness ( J:206074 )

• decreased skin stretching (stiff skin)

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

adipose tissue

decreased subcutaneous adipose tissue amount ( J:206074 )

• by 3 months

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

hematopoietic system

increased B cell number ( J:206074 )

• infiltration of activated B cells and plasma cells in the dermis

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased plasma cell number ( J:206074 )

• infiltration of activated B cells and plasma cells in the dermis

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

abnormal T-helper 1 cell morphology ( J:206074 )

• dermal polarization towards pro-inflammatory T helper cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic scleroderma		DOID:418	OMIM:181750	J:206074

Genotype
MGI:5558879

ht8

• Allelic Composition: Fbn1^tm2.1Hcd/Fbn1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

immune system

increased B cell number ( J:206074 )

• infiltration of activated B cells and plasma cells in the dermis

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

increased plasma cell number ( J:206074 )

• nfiltration of activated B cells and plasma cells in the dermis

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal T-helper 1 cell morphology ( J:206074 )

• dermal polarization towards pro-inflammatory T helper cells

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal interleukin secretion ( J:206074 )

• increased IL9, IL13 and IL22 in CD3+ dermal cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased interleukin-13 secretion ( J:206074 )

• in CD3+ dermal cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased interleukin-9 secretion ( J:206074 )

• in CD3+ dermal cells

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased autoantibody level ( J:206074 )

• increased anti-nuclear and anti-topoisomerase I antibody levels

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

increased anti-nuclear antigen antibody level ( J:206074 )

• however, auto-antibody levels are normalized by treatment with an integrin beta1 activating

integument

decreased subcutaneous adipose tissue amount ( J:206074 )

• by 3 months

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal cutaneous collagen fibril morphology ( J:206074 )

• increased by 1 month

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal dermal layer morphology ( J:206074 )

• disorganized and excessive microfibrillar aggregates in the dermis with sparsely distributed elastin

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

increased skin stiffness ( J:206074 )

• decreased skin stretching (stiff skin)

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

adipose tissue

decreased subcutaneous adipose tissue amount ( J:206074 )

• by 3 months

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

hematopoietic system

increased B cell number ( J:206074 )

• infiltration of activated B cells and plasma cells in the dermis

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

increased plasma cell number ( J:206074 )

• nfiltration of activated B cells and plasma cells in the dermis

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

abnormal T-helper 1 cell morphology ( J:206074 )

• dermal polarization towards pro-inflammatory T helper cells

• however, skin condition is normalized by treatment with an integrin beta1 activating or TGF-beta-neutralizing antibody

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic scleroderma		DOID:418	OMIM:181750	J:206074

Genotype
MGI:4880671

ht9

• Allelic Composition: Fbn1^tm1Lper/Fbn1⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CD-1

cardiovascular system

abnormal aorta tunica media morphology ( J:167276 )

• at 9 months, aortic media is thickened compared to in wild-type mice

• Background Sensitivity: however, mice on a C57BL/6 congenic background are asymptomatic at 3 months unlike mice on a 129/Sv congenic background

respiratory system

emphysema ( J:167276 )

• Background Sensitivity: at 3 months, expanded alveoli in mice on a C57BL/6 congenic background are milder than in mice on a 129/Sv congenic background

• at 6 months, mice exhibit severely expanded alveoli compared with wild-type mice

skeleton

abnormal skeleton morphology ( J:167276 )

• Background Sensitivity: skeletal manifestations (measured by ratio between the linear distance and the length from the first cervical vertebrae to the last thoracic vertebrae) in mice on a C57BL/6 congenic background are milder than in mice on a 129/Sv congenic background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:167276

Genotype
MGI:4880670

ht10

• Allelic Composition: Fbn1^tm1Lper/Fbn1⁺
• Genetic Background: involves: 129/Sv * CD-1

mortality/aging

premature death ( J:167276 )

• at 3 months with hemothorax

respiratory system

hemothorax ( J:167276 )

lung inflammation ( J:167276 )

• chronic

abnormal lung morphology ( J:167276 )

• at 3 months, pulmonary alterations in mice on a 129/Sv congenic background are stronger than in mice on a C57BL/6 congenic background

• mice on a congenic 129/Sv background exhibit wide clinical variability

abnormal respiratory bronchiole morphology ( J:167276 )

• mice exhibit enlarged peripheral air space (respiratory bronchioles and alveoli) compared with wild-type mice

emphysema ( J:167276 )

• mice exhibit enlarged peripheral air space (respiratory bronchioles and alveoli) compared with wild-type mice

cardiovascular system

abnormal aorta tunica media morphology ( J:167276 )

• aortic media is thickened compared to in wild-type mice

• Background Sensitivity: at 3 months, enlarged media in mice on a 129/Sv congenic background is stronger than in mice on a C57BL/6 congenic background

• mice on a congenic 129/Sv background exhibit wide clinical variability

abnormal aorta elastic fiber morphology ( J:167276 )

hemothorax ( J:167276 )

skeleton

abnormal skeleton morphology ( J:167276 )

• Background Sensitivity: skeletal manifestations (measured by the ratio between the linear distance and the length from the first cervical vertebrae to the last thoracic vertebrae) in mice on a 129/Sv congenic background are stronger than in mice on a C57BL/6 congenic background

• mice on a congenic 129/Sv background exhibit wide clinical variability

kyphosis ( J:167276 )

• at 2 months

immune system

lung inflammation ( J:167276 )

• chronic

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:167276

Genotype
MGI:4839089

ht11

• Allelic Composition: Fbn1^tm1.2Lysa/Fbn1⁺
• Genetic Background: involves: C57BL/6

Fragmentation of aortic root elastic lamellae in Fbn1^tm1.2Lysa/Fbn1⁺ mice

cardiovascular system

abnormal aorta elastic fiber morphology ( J:165897 )

• at 2 months, mice exhibit progressive fragmentation of the aortic elastic lamellae with age unlike wild-type mice

muscle

abnormal skeletal muscle fiber morphology ( J:165897 )

• at P8, mice exhibit fragmentation of the microfibril network unlike in wild-type mice

• however, early postnatal assembly of microfibril networks is normal

abnormal tendon morphology ( J:165897 )

• at P8, mice exhibit fragmentation of the microfibril network unlike in wild-type mice

• however, early postnatal assembly of microfibril networks is normal

skeleton

abnormal tendon morphology ( J:165897 )

• at P8, mice exhibit fragmentation of the microfibril network unlike in wild-type mice

• however, early postnatal assembly of microfibril networks is normal

integument

abnormal cutaneous microfibril morphology ( J:165897 )

• at P8, mice exhibit fragmentation of the microfibril network unlike in wild-type mice

• however, early postnatal assembly of microfibril networks is normal

Genotype
MGI:5313384

ht12

• Allelic Composition: Fbn1^tm3.2Lysa/Fbn1⁺
• Genetic Background: Not Specified

Thick skin in Fbn1^tm3.2Lysa/Fbn1⁺ and Fbn1^tm3.2Lysa/Fbn1^tm3.2Lysa mice

integument

decreased subcutaneous adipose tissue amount ( J:181493 )

abnormal skin morphology ( J:181493 )

• mice exhibit thickened and less elastic skin compared to in wild-type mice

abnormal dermal layer morphology ( J:181493 )

• excessive collagen deposition

thick dermal layer ( J:181493 )

thick skin ( J:181493 )

• persisting through old age

limbs/digits/tail

brachyphalangia ( J:181493 )

• short proximal and distal phalanges in the fore and hind paws at 3 to 4 weeks of age

short metacarpal bones ( J:181493 )

• at 3 to 4 weeks of age

adipose tissue

decreased subcutaneous adipose tissue amount ( J:181493 )

cardiovascular system

cardiovascular system phenotype ( J:181493 )

N • in contrast to Fbn1-targeted mouse models of Marfan Syndrome, aortic root morphology is normal

skeleton

brachyphalangia ( J:181493 )

• short proximal and distal phalanges in the fore and hind paws at 3 to 4 weeks of age

short metacarpal bones ( J:181493 )

• at 3 to 4 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Marfan syndrome	DOID:14323	OMIM:154700	J:181493
Weill-Marchesani syndrome		DOID:0050475	OMIM:277600 OMIM:608328 OMIM:613195 OMIM:614819 OMIM:PS277600	J:181493

Genotype
MGI:3721113

cx13

• Allelic Composition: Fbn1^Tsk Bloc1s6⁺/Fbn1⁺ Bloc1s6^pa
• Genetic Background: B6.Cg-Fbn1^Tsk +/+ Bloc1s6^pa/J

cellular

cellular phenotype ( J:55591 )

N • immunohistochemistry of endothelial cells from interscapular skin sections does not show indication of abnormal apoptosis, a symptom found in human scleroderma

hematopoietic system

hematopoietic system phenotype ( J:29151 )

N • no aberrant bleeding time after tail vein nick

cardiovascular system

abnormal vascular endothelial cell physiology ( J:81020 )

abnormal vasodilation ( J:81020 )

muscle

abnormal vasodilation ( J:81020 )

Genotype
MGI:3652417

cx14

• Allelic Composition: Fbn1^tm3Rmz/Fbn1⁺; Fbn2^tm1Rmz/Fbn2^tm1Rmz
• Genetic Background: involves: 129

Fbn1^tm3Rmz/Fbn1^tm3Rmz Fbn2^tm1Rmz/Fbn2^tm1Rmz and Fbn1^tm3Rmz/Fbn1⁺ Fbn2^tm1Rmz/Fbn2^tm1Rmz mice show poor organization of the aorta wall

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:110586 )

• about 50% die after E14.5

cardiovascular system

abnormal aorta tunica media morphology ( J:110586 )

• at E14.5 expression analysis indicates impaired or delayed matrix assembly in the medial layer of the aorta

Genotype
MGI:5444488

cx15

• Allelic Composition: Fbn1^tm1Hcd/Fbn1⁺; Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal aorta wall morphology ( J:188799 )

• elastic fiber fragmentation and greater collagen deposition within the medial compartment of the aortic wall is increased compared to either single heterozygote

dilated aorta bulb ( J:188799 )

• mutants show an increase in aortic root dimension at 2 and 4 months of age compared to either single heterozygote

• aortic dilatation is specific to the aortic root

aortic aneurysm ( J:188799 )

• aortic root aneurysm

growth/size/body

growth/size/body region phenotype ( J:188799 )

N • mutants exhibit normal body size and growth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Loeys-Dietz syndrome		DOID:0050466		J:188799

Genotype
MGI:5558883

cx16

• Allelic Composition: Fbn1^tm3.1Hcd/Fbn1⁺; Itgb3^tm1Hyn/Itgb3⁺
• Genetic Background: involves: 129S * 129X1/SvJ * C57BL/6J * FVB/N

integument

integument phenotype ( J:206074 )

N • skin stiffness and collagen deposition are normalized at 3 months

abnormal cutaneous collagen fibril morphology ( J:206074 )

• increased collagen in the dermis of some mice at 5 months as in Itgb3-deficient mice

thick dermal layer ( J:206074 )

• in some mice at 5 months as in Itgb3-deficient mice

epidermal hyperplasia ( J:206074 )

• focal in some mice at 5 months as in Itgb3-deficient mice

Genotype
MGI:5558881

cx17

• Allelic Composition: Fbn1^tm2.1Hcd/Fbn1⁺; Itgb3^tm1Hyn/Itgb3⁺
• Genetic Background: involves: 129S * 129X1/SvJ * C57BL/6J * FVB/N

integument

integument phenotype ( J:206074 )

N • skin stiffness and collagen deposition are normalized at 3 months

abnormal cutaneous collagen fibril morphology ( J:206074 )

• increased collagen in the dermis of some mice at 5 months as in Itgb3-deficient mice

thick dermal layer ( J:206074 )

• in some mice at 5 months as in Itgb3-deficient mice

epidermal hyperplasia ( J:206074 )

• focal in some mice at 5 months as in Itgb3-deficient mice

Genotype
MGI:5301099

cx18

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Stat6^tm1Gru/Stat6^tm1Gru
• Genetic Background: involves: 129S2/SvPas * C57BL/10 * DBA/2

immune system

decreased interleukin-4 secretion ( J:57957 )

• no Il4 is produced by Th2 cells

integument

integument phenotype ( J:57957 )

N • no skin fibrosis develops

respiratory system

emphysema ( J:57957 )

• emphysema develops as expected for heterozygous Fbn1^Tsk

Genotype
MGI:3800678

cx19

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Tgfb1^tm1N/Tgfb1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6J * C57BL/10 * DBA/2

respiratory system

overexpanded pulmonary alveolus ( J:68448 )

• enlarged alveoli and a histologic picture of emphysema are found, similar to that seen in tight skin heterozygotes with normal TGFB1 expression

immune system

immune system phenotype ( J:68448 )

N • unlike tight skin mice, these compound mutants do not develop autoantibodies against the scleroderma antigens topoisomerase I and fibrillin 1

integument

abnormal cutaneous collagen fibril morphology ( J:68448 )

• electron micrographs of skin show a predominance of abnormally small diameter collagen fibers, the skin is slightly thicker than normal but not as thick as in tight skin mutants with normal TGFB1 expression, and the fat tissue and hair follicles are preserved

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary emphysema		DOID:9675	OMIM:130700	J:68448

Genotype
MGI:3800993

cx20

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Tgfb1^tm1N/Tgfb1^tm1N
• Genetic Background: involves: 129S/SvEv * C57BL/6J * C57BL/10 * DBA/2

mortality/aging

prenatal lethality ( J:68448 )

• absence of tight skin heterozygous Tgfb1 null pups from several crosses of heterozygotes is indicative of embryonic loss

Genotype
MGI:4839090

cx21

• Allelic Composition: Fbn1^tm1.2Lysa/Fbn1⁺; Fbn2^tm1Rmz/Fbn2^tm1Rmz
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:165897 )

• most mice die right after birth especially when the dam is homozygous for Fbn2^tm1Rmz

prenatal lethality, incomplete penetrance ( J:165897 )

• especially when the dam is homozygous for Fbn2^tm1Rmz

Genotype
MGI:3800676

cx22

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Il4ra^tm1Sz/Il4ra⁺
• Genetic Background: involves: BALB/cJ * C57BL/6J * C57BL/10 * DBA/2

respiratory system

overexpanded pulmonary alveolus ( J:68448 )

• enlarged alveoli and a histologic picture of emphysema are found, similar to that seen in tight skin heterozygotes that are wildtype for Il4ra

immune system

increased autoantibody level ( J:68448 )

• increased anti-topoisomerase antibodies relative to wildtype, but lower than in tight skin mice wildtype for Il4ra

integument

thick skin ( J:68448 )

• the skin is as thick as tight skin heterozygotes wildtype for Il4ra

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary emphysema		DOID:9675	OMIM:130700	J:68448

Genotype
MGI:3800675

cx23

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Il4ra^tm1Sz/Il4ra^tm1Sz
• Genetic Background: involves: BALB/cJ * C57BL/6J * C57BL/10 * DBA/2

respiratory system

overexpanded pulmonary alveolus ( J:68448 )

• enlarged alveoli and a histologic picture of emphysema are found, similar to that seen in tight skin heterozygotes with normal IL4RA expression

immune system

immune system phenotype ( J:68448 )

N • unlike tight skin mice, these compound mutants do not develop autoantibodies against the scleroderma antigens topoisomerase I and fibrillin 1

integument

integument phenotype ( J:68448 )

N • the cutaneous hyperplasia found in tight skin heterozygotes is diminished in these compound mutants and the thickness of the skin is normal

abnormal cutaneous collagen fibril morphology ( J:68448 )

• electron micrographs of skin show a predominance of abnormally small diameter collagen fibers, although there is reduced fibrotic development compared with tight skin mice with wildtype expression of IL4RA

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary emphysema		DOID:9675	OMIM:130700	J:68448

Genotype
MGI:5301105

cx24

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Tg(Tcra2C,Tcrb2C)1Dlo/?
• Genetic Background: involves: C57BL/10 * DBA/2

integument

integument phenotype ( J:57957 )

N • dermal fibrosis fails to develop

respiratory system

emphysema ( J:57957 )

• emphysema develops as expected for heterozygous Fbn1^Tsk

Genotype
MGI:5301104

cx25

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Tg(TcraH-Y,TcrbH-Y)71Vbo/?
• Genetic Background: involves: C57BL/10 * DBA/2

integument

integument phenotype ( J:57957 )

N • no skin fibrosis develops

respiratory system

emphysema ( J:57957 )

• emphysema develops as expected for heterozygous Fbn1^Tsk

Genotype
MGI:5301103

cx26

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Il4^tm1Nnt/Il4^tm1Nnt
• Genetic Background: involves: C57BL/6 * C57BL/10 * DBA/2

immune system

decreased interleukin-4 secretion ( J:57957 )

• no Il4 is produced by Th2 cells

integument

integument phenotype ( J:57957 )

N • no skin fibrosis develops

respiratory system

emphysema ( J:57957 )

• emphysema develops as expected for heterozygous Fbn1^Tsk

Genotype
MGI:3619906

cx27

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Kit^W/Kit⁺
• Genetic Background: involves: C57BL/6 * C57BL/10 * DBA/2 * WB/ReJ

pigmentation

diluted coat color ( J:24076 )

• variable amounts of white-spotting on a slightly diluted coat color

variable body spotting ( J:24076 )

• variable amounts of white-spotting on a slightly diluted coat color

integument

diluted coat color ( J:24076 )

• variable amounts of white-spotting on a slightly diluted coat color

variable body spotting ( J:24076 )

• variable amounts of white-spotting on a slightly diluted coat color

tight skin ( J:24076 )

skin fibrosis ( J:24076 )

• progressive development of skin fibrosis similar to that seen in single heterozygous Fbn1 mutant mice

Genotype
MGI:3619905

cx28

• Allelic Composition: Fbn1^Tsk/Fbn1⁺; Kit^W/Kit^W-v
• Genetic Background: involves: C57BL/6 * C57BL/10 * DBA/2 * WB/ReJ

hematopoietic system

anemia ( J:24076 )

absent mast cells ( J:24076 )

• absence of interscapular skin mast cells

respiratory system

overexpanded pulmonary alveolus ( J:24076 )

• enlargement of airspaces

immune system

absent mast cells ( J:24076 )

• absence of interscapular skin mast cells

pigmentation

absent coat pigmentation ( J:24076 )

• white coat and black eyes

integument

absent coat pigmentation ( J:24076 )

• white coat and black eyes

abnormal hypodermis morphology ( J:24076 )

• increase in subcutaneous connective tissue, with an accumulation beneath the panniculus carnosus muscle

tight skin ( J:24076 )

• tight skin develops around 7 days of age

skin fibrosis ( J:24076 )

• develop skin fibrosis, indicating that fibrosis is mast cell independent, however the degree of fibrosis development at older ages (5-7 months) is less than in single heterozygous Fbn1 mutant mice, which contain elevated levels of mast cells, indicating that mast cells contribute to fibrosis later in life