Phenotypes associated with this allele

• Allele Symbol: Hoxa5^tm1Rob
• Allele Name: targeted mutation 1, Elizabeth J Robertson
• Allele ID: MGI:2150397
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hoxa5^tm1Rob/Hoxa5^tm1Rob	129S(Cg)-Hoxa5^tm1Rob	MGI:3612385
hm2	Hoxa5^tm1Rob/Hoxa5^tm1Rob	B6.129S(Cg)-Hoxa5^tm1Rob	MGI:3612387
hm3	Hoxa5^tm1Rob/Hoxa5^tm1Rob	involves: 129S/SvEv * C57BL/6 * MF1	MGI:4941623
hm4	Hoxa5^tm1Rob/Hoxa5^tm1Rob	involves: 129S/SvEv * MF1	MGI:3028504
cx5	Hoxa5^tm1Rob/Hoxa5^tm1Rob Pdgfra^tm11(EGFP)Sor/Pdgfra^+	involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * MF1	MGI:4941631
cx6	Hoxa5^tm1Rob/Hoxa5^+ Hoxa6^tm1Mrc/Hoxa6^+ Hoxb5^tm1Mrc/Hoxb5^+ Hoxb6^tm1Mrc/Hoxb6^+ Hoxc5^tm1Mrc/Hoxc5^+ Hoxc6^tm1Dds/Hoxc6^+	involves: 129S/SvEv * 129S7/SvEvBrd	MGI:4358354
cx7	Hoxa5^tm1Rob/Hoxa5^tm1Rob Hoxb5^tm1Mrc/Hoxb5^tm1Mrc Hoxc5^tm1Mrc/Hoxc5^tm1Mrc	involves: 129S/SvEv * 129S7/SvEvBrd	MGI:4358348

Genotype
MGI:3612385

hm1

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob
• Genetic Background: 129S(Cg)-Hoxa5^tm1Rob

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:45341 )

• a little less than half die by weaning with 85% of those deaths occuring within 24 hours of birth

postnatal lethality, incomplete penetrance ( J:45341 )

• Background Sensitivity: a little less than half die by weaning

• some mice survive to adulthood and are fertile; however, survivors display limited growth and delayed eye opening

skeleton

abnormal cricoid cartilage morphology ( J:45341 )

• the cricoid is always larger than the thyroid cartilage due to fusion with the first tracheal rings

cricoid and tracheal cartilage fusion ( J:45341 )

• the cricoid cartilage is fused with the first tracheal rings

abnormal tracheal cartilage morphology ( J:45341 )

• tracheal rings do not display a normal banding pattern

• the cartilage does not not extend as dorsally as in wild-type

decreased tracheal cartilage ring number ( J:45341 )

respiratory system

abnormal larynx morphology ( J:45341 )

• disorganized larynx morphology

abnormal cricoid cartilage morphology ( J:45341 )

• the cricoid is always larger than the thyroid cartilage due to fusion with the first tracheal rings

abnormal branching involved in lung morphogenesis ( J:45341 )

• reduced branching of the bronchial tree associated with disorganization of the surrounding mesenchyme

impaired branching involved in respiratory bronchiole morphogenesis ( J:45341 )

• at E15.5, the number of bronchioli per area scored is reduced by 33%

abnormal lung saccule morphology ( J:45341 )

• thickened alveolar walls at the saccular stage (E17.5-E18.5)

abnormal bronchus epithelium morphology ( J:45341 )

• cellular disorganization in the bronchial epithelial lining and underlying lamina propria

abnormal pulmonary acinus morphology ( J:45341 )

• at E15.5, the number of terminal acini per area scored is reduced by 33%

• the diameter of terminal acini is generally reduced in size

atelectasis ( J:45341 )

• high proportion of collapsed lungs at autopsy

• at birth, fluid-filled bronchioli and alveoli are observed

abnormal bronchiole morphology ( J:45341 )

• at E15.5, the diameter of bronchioli is generally reduced in size

abnormal bronchiole epithelium morphology ( J:45341 )

• cellular disorganization in the bronchiolar epithelial lining and underlying lamina propria

abnormal trachea morphology ( J:45341 )

• disorganized tracheal epithelium and adjacent submucosa and thickened lamina propria, with variable expressivity

• tracheal epithelium appears to be stratified rather than pseudostratified

• wider lamina propria along the entire length of trachea

abnormal tracheal cartilage morphology ( J:45341 )

• tracheal rings do not display a normal banding pattern

• the cartilage does not not extend as dorsally as in wild-type

cricoid and tracheal cartilage fusion ( J:45341 )

• the cricoid cartilage is fused with the first tracheal rings

decreased tracheal cartilage ring number ( J:45341 )

trachea occlusion ( J:45341 )

• tracheal occlusion in severely affected mice

trachea stenosis ( J:45341 )

• narrowing of the trachea with severe reduction in the lumen diameter

respiratory distress ( J:45341 )

• most pups display respiratory disterss immediately after birth

decreased surfactant secretion ( J:84449 )

• reduced levels of pulmonary surfactant proteins

digestive/alimentary system

abnormal digestive secretion ( J:58676 )

• delayed maturation of the secretion pattern of digestive enzymes for disaccharides

meteorism ( J:45341 )

• air in stomach and intestines at death

vision/eye

delayed eyelid opening ( J:45341 , J:84449 )

• in mice surviving to adulthood (J:45341)

• by about 7 days (J:84449)

hearing/vestibular/ear

delayed ear emergence ( J:84449 )

• delayed ear elevation by approximately 1.5 days

growth/size/body

delayed ear emergence ( J:84449 )

• delayed ear elevation by approximately 1.5 days

meteorism ( J:45341 )

• air in stomach and intestines at death

ovary cyst ( J:182519 )

♀ • at 10 months of age, 5 of 8 ovaries from nulliparous female homozygotes contain large fluid-filled epithelial cysts; in contrast, only two small cysts are detected in 1of 5 control ovaries

♀ • immunolabeling studies suggest that these ovarian epithelial inclusion cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas

♀ • staining by ovarian cancer markers supports the notion that these cysts may represent preneoplastic lesions

♀ • at 10 months of age, estrous acyclicity and presence of ovarian epithelial cysts correlate with a reduced expression of specific EGFR signaling components

♀ • however, 4- and 10-month-old nulliparous females exhibit normal ovarian folliculogenesis at diestrus

♀ • similarly, ovarian histology of pregnant female homozygotes is normal

postnatal growth retardation ( J:45341 , J:84449 )

• in mice surviving to adulthood (J:45341)

• between 13 and 35 days after birth (J:84449)

• size differential decreases after 5 weeks of age and is only 2% by age 84 days (J:84449)

endocrine/exocrine glands

abnormal thyroid gland development ( J:84449 )

• thyroid follicles slightly disorganized at E16.5

• large proportion of empty or incompletely filled follicles at E17.5-E18.5

• thyroid normal at birth through 30 days of age but follicle diameter decreased 15% at 30 days of age

ovary cyst ( J:182519 )

♀ • at 10 months of age, 5 of 8 ovaries from nulliparous female homozygotes contain large fluid-filled epithelial cysts; in contrast, only two small cysts are detected in 1of 5 control ovaries

♀ • immunolabeling studies suggest that these ovarian epithelial inclusion cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas

♀ • staining by ovarian cancer markers supports the notion that these cysts may represent preneoplastic lesions

♀ • at 10 months of age, estrous acyclicity and presence of ovarian epithelial cysts correlate with a reduced expression of specific EGFR signaling components

♀ • however, 4- and 10-month-old nulliparous females exhibit normal ovarian folliculogenesis at diestrus

♀ • similarly, ovarian histology of pregnant female homozygotes is normal

homeostasis/metabolism

increased circulating estradiol level ( J:182519 )

♀ • at 10 months of age, nulliparous females exhibit a 2-fold increase in serum 17beta-estradiol concentrations at estrus relative to wild-type controls

increased circulating thyroid-stimulating hormone level ( J:84449 )

• elevated TSH levels at 15 days of age but not at 17 days

cyanosis ( J:45341 )

• most dead pups display cyanotic skin

craniofacial

delayed ear emergence ( J:84449 )

• delayed ear elevation by approximately 1.5 days

reproductive system

ovary cyst ( J:182519 )

♀ • at 10 months of age, 5 of 8 ovaries from nulliparous female homozygotes contain large fluid-filled epithelial cysts; in contrast, only two small cysts are detected in 1of 5 control ovaries

♀ • immunolabeling studies suggest that these ovarian epithelial inclusion cysts originate from the ovarian surface epithelium, a source of epithelial ovarian carcinomas

♀ • staining by ovarian cancer markers supports the notion that these cysts may represent preneoplastic lesions

♀ • at 10 months of age, estrous acyclicity and presence of ovarian epithelial cysts correlate with a reduced expression of specific EGFR signaling components

♀ • however, 4- and 10-month-old nulliparous females exhibit normal ovarian folliculogenesis at diestrus

♀ • similarly, ovarian histology of pregnant female homozygotes is normal

early sexual maturation ( J:182519 )

♀ • nulliparous females display precocious puberty, with the first estrus observed earlier (day 31.9) relative to wild-type controls (day 34.4)

♀ • notably, vaginal opening occurs at similar ages for mutant and control females

abnormal estrous cycle ( J:182519 )

♀ • nulliparous female homozygotes display an early onset of estrous acyclicity

♀ • starting at 4.5-6 months of age, nulliparous females show a significant decrease in the number of cycles per month with a lengthened diestrus period

♀ • by 8-10 months of age, nulliparous females show prolonged diestrus and metestrus periods with a reduced estrus duration leading to a further decrease in the number of estruses per month

♀ • however, at 8-10 months of age, all female homozygotes are fertile with a mean litter size that is comparable to that of wild-type controls

prolonged diestrus ( J:182519 )

♀ • starting at 4.5-6 months of age

short estrus ( J:182519 )

♀ • by 8-10 months of age

prolonged metestrus ( J:182519 )

♀ • by 8-10 months of age

prolonged estrous cycle ( J:182519 )

♀ • nulliparous females show a prolonged estrous cycle with increased metestrus-diestrus length that worsens with age

Genotype
MGI:3612387

hm2

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob
• Genetic Background: B6.129S(Cg)-Hoxa5^tm1Rob

mortality/aging

neonatal lethality, incomplete penetrance ( J:45341 )

• 85% of mice that die, die within 24 hours of birth

postnatal lethality, incomplete penetrance ( J:45341 )

• Background Sensitivity: few survivors (3%) at weaning, unlike mice on an inbred 129 background where about 16% survive to weaning

skeleton

abnormal cricoid cartilage morphology ( J:45341 )

• always larger than thyroid cartilage

decreased tracheal cartilage ring number ( J:45341 )

respiratory system

abnormal cricoid cartilage morphology ( J:45341 )

• always larger than thyroid cartilage

impaired branching involved in bronchus morphogenesis ( J:45341 )

• reduced branching of the bronchial tree

atelectasis ( J:45341 )

• high proportion of collapsed lungs at autopsy

thick pulmonary interalveolar septum ( J:45341 )

• thickened alveolar walls and areas of poorly inflated alveoli

abnormal trachea morphology ( J:45341 )

• disorganized tracheal epithelium and a thickened lamina propria

decreased tracheal cartilage ring number ( J:45341 )

trachea occlusion ( J:45341 )

• tracheal occlusion frequent

decreased surfactant secretion ( J:45341 )

• reduced levels of pulmonary surfactant proteins

vision/eye

delayed eyelid opening ( J:45341 )

• in mice surviving to adulthood

growth/size/body

meteorism ( J:45341 )

• air in stomach and intestines at death

postnatal growth retardation ( J:45341 )

• in mice surviving to adulthood

digestive/alimentary system

meteorism ( J:45341 )

• air in stomach and intestines at death

Genotype
MGI:4941623

hm3

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob
• Genetic Background: involves: 129S/SvEv * C57BL/6 * MF1

respiratory system

lung inflammation ( J:113378 )

• chronic lung inflammation, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells is observed

• a significantly higher number of macrophages, lymphocytes and neutrophils is detected in the bronchoalveolar lavage fluid (BALF) relative to that in wild-type controls

• mutant BALF contains large, vacuolated macrophages with dark inclusions, not seen in control samples

• most macrophages stain positively for MMP-12, suggesting increased elastase production in mutant lungs

• inflammatory response is associated with slightly elevated MMP2 and MMP9 activities in alveolar macrophage-conditioned medium

impaired lung alveolus development ( J:113378 )

• at P5, very few growing septa are observed, indicating impaired alveolar septation

• at P15, only some alveoli are formed unlike in wild-type lungs

abnormal lung weight ( J:113378 )

• at P0, P5, and P15, the lung weight/body weight ratio is lower than that in wild-type controls; however, this difference is resolved by P31

• lung proliferation is initially reduced (P0 and P5) but subsequently higher than that in wild-type lungs (P15 and P31), with no significant differences noted at P60

• no significant differences in lung apoptosis are observed at any postnatal stage tested

abnormal pulmonary alveolus morphology ( J:113378 )

• at P31, some areas of mutant lungs are completely depleted of alveoli, whereas others display large tubular structures

atelectasis ( J:113378 )

• at P0, mutant lungs are collapsed unlike wild-type lungs

• at P15 and P31, areas of atelectasis are observed

overexpanded pulmonary alveolus ( J:113378 )

• at P15, enlarged distal airspaces are observed

abnormal pulmonary interalveolar septum morphology ( J:113378 )

• at P5, very few growing septa are observed unlike in wild-type lungs

emphysema ( J:113378 )

• at P31 and P60, an emphysema-like phenotype is observed

abnormal pulmonary alveolar parenchyma morphology ( J:113378 )

• at P0, mutant lungs are collapsed with a thickened parenchymal layer

• at P5 and P15, alveolar myofibroblasts are abnormally trapped in the parenchyma surrounding alveoli rather than found at the tip of the growing septa as in wild-type lungs

• abnormal positioning of alveolar myofibroblasts results in improper elastin deposition and septa formation

abnormal alveolar macrophage morphology ( J:113378 )

• a significantly higher percentage of alveolar macrophages is observed from birth to adulthood, except for P15

• at P31 and P60, an accumulation of vacuolated (hypertrophic and foamy) alveolar macrophages is observed, indicating an inflammatory response

increased type II pneumocyte number ( J:113378 )

• at P31, a small but significant increase in the number of Foxa2-positive type II pneumocytes is observed

abnormal pulmonary elastic fiber morphology ( J:113378 )

• at P0 and P5, pulmonary elastic fibers appear tangled in the parenchyma

• at P15 onwards, elastic fibers appear more abundant, disorganized and fragmented than in wild-type lungs

abnormal respiratory mucosa goblet cell morphology ( J:113378 )

• ectopic goblet cells are detected in distal structures such as the secondary bronchi and bronchioles, unlike in wild-type lungs

• specification of goblet cells is altered, resulting in hyperplasia, metaplasia, and mucus hypersecretion from P15 onwards

increased respiratory mucosa goblet cell number ( J:113378 )

• a striking increase in goblet cell number is noted along the epithelium of the trachea and the primary bronchi from P15 onwards, unlike in wild-type lungs

• increased goblet cell numbers are already evident at E18.5

abnormal surfactant secretion ( J:113378 )

• reduced surfactant protein production as a result of decreased surfactant protein gene expression, not due to a change in cellularity

immune system

abnormal alveolar macrophage morphology ( J:113378 )

• a significantly higher percentage of alveolar macrophages is observed from birth to adulthood, except for P15

• at P31 and P60, an accumulation of vacuolated (hypertrophic and foamy) alveolar macrophages is observed, indicating an inflammatory response

lung inflammation ( J:113378 )

• chronic lung inflammation, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells is observed

• a significantly higher number of macrophages, lymphocytes and neutrophils is detected in the bronchoalveolar lavage fluid (BALF) relative to that in wild-type controls

• mutant BALF contains large, vacuolated macrophages with dark inclusions, not seen in control samples

• most macrophages stain positively for MMP-12, suggesting increased elastase production in mutant lungs

• inflammatory response is associated with slightly elevated MMP2 and MMP9 activities in alveolar macrophage-conditioned medium

hematopoietic system

abnormal alveolar macrophage morphology ( J:113378 )

• a significantly higher percentage of alveolar macrophages is observed from birth to adulthood, except for P15

• at P31 and P60, an accumulation of vacuolated (hypertrophic and foamy) alveolar macrophages is observed, indicating an inflammatory response

Genotype
MGI:3028504

hm4

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob
• Genetic Background: involves: 129S/SvEv * MF1

mortality/aging

postnatal lethality, incomplete penetrance ( J:15576 )

• proportions of homozygotes normal at E18.5

• most deaths within 4 days after birth

• survivors lack overt phenotype and are fertile

skeleton

increased sternebra number ( J:15576 )

• extra sternebrae in 9% of homozygotes, develops from manubrium

sternebra fusion ( J:15576 )

• some cases of fusion of adjacent sternebrae

asymmetric sternocostal joints ( J:15576 )

• irregularities in sternocostal attachments

abnormal rib morphology ( J:15576 )

increased rib number ( J:15576 )

• C7 rib development extensive on one or both sides

• L1 ribs in 19% of individuals

rib fusion ( J:15576 )

• one third of C7 ribs were fused ventrally with first thoracic rib but occasionally make independent contact with sternum

abnormal vertebrae morphology ( J:15576 )

cervical vertebral transformation ( J:15576 )

• C7 ribs in 73% of homozygotes at birth

• percent of C7 ribs lower in homozygotes surviving to adulthood

• absence of tuberulum anterior on C6 making it more similar to C3, C4, C5

lumbar vertebral transformation ( J:15576 )

• L1 ribs in 19% of individuals

Genotype
MGI:4941631

cx5

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob; Pdgfra^{tm11(EGFP)Sor}/Pdgfra⁺
• Genetic Background: involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * MF1

respiratory system

abnormal pulmonary alveolar parenchyma morphology ( J:113378 )

• at E16.5, most alveolar myofibroblast progenitors fail to spread distally and remain clustered around the epithelium, unlike in wild-type lungs where progenitors are dispersed in the lung parenchyma

• alveolar myofibroblast progenitors also fail to invade some regions of the developing lung

cellular

abnormal cell migration ( J:113378 )

• wounding assays performed on primary mesenchymal cells isolated from E15.5 lungs revealed that, unlike wild-type cells which invade the wounded area within 12 hrs and fill the gap by 24 hrs, mutant cells display reduced migration at both time points

• however, no difference in migratory behavior is observed in response to gelatin in Boyden chambers

Genotype
MGI:4358354

cx6

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5⁺; Hoxa6^tm1Mrc/Hoxa6⁺; Hoxb5^tm1Mrc/Hoxb5⁺; Hoxb6^tm1Mrc/Hoxb6⁺; Hoxc5^tm1Mrc/Hoxc5⁺; Hoxc6^tm1Dds/Hoxc6⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd

skeleton

abnormal skeleton morphology ( J:124112 )

• primaxial and abaxial skeleton defects are less severe than in either triple homozygote

Genotype
MGI:4358348

cx7

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob; Hoxb5^tm1Mrc/Hoxb5^tm1Mrc; Hoxc5^tm1Mrc/Hoxc5^tm1Mrc
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd

skeleton

abnormal axial skeleton morphology ( J:124112 )

• the clavicles are attached to the rib cage by connective tissue and do not articulate directly with it unlike in wild-type mice

absent sternal manubrium ( J:124112 )

short sternum ( J:124112 )

abnormal rib joint morphology ( J:124112 )

• a eighth rib is attached to the sternum unlike in wild-type mice

• T1 ribs exhibit incomplete projection and T2 ribs extend but often do not reach the sternum (in 64% of mice)

• however, rib attachment posterior to T1 is normal

abnormal rib development ( J:124112 )

• ribs initiate but do not extend on T1 unlike in wild-type mice

decreased rib number ( J:124112 )

• mice are missing a complete first rib

rib fusion ( J:124112 )

• rib 2 and 3 are fused prior to attachment to the sternum

small thoracic cage ( J:124112 )

abnormal intervertebral disk morphology ( J:124112 )

• dorsal cartilage is thickened and forms a distinct curvature at the top of the vertebra unlike in wild-type mice

cervical vertebral fusion ( J:124112 )

vertebral transformation ( J:124112 )

• C3 through T2 exhibit anterior homeotic transformations

• C3 through T1 exhibit characteristics of C2

• however, posterior thoracic, lumbar, and sacral vertebrae are normal in appearance and position

thoracic vertebral transformation ( J:124112 )

• C3 through T1 exhibit characteristics of C2

• T2 lacks anterior projections and is similar to T3

• ibs do not extend on T1 unlike in wild-type mice

cervical vertebral transformation ( J:124112 )

• C3 through T1 exhibit characteristics of C2

• vertebral foramina extend beyond C6 to C7 unlike in wild-type mice